PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32049373-0 2020 Mechanistic Insights into the Regio- and Stereoselectivities of Testosterone and Dihydrotestosterone Hydroxylation Catalyzed by CYP3A4 and CYP19A1. Testosterone 64-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 128-134 33826998-4 2021 In the present quantitative study, we investigated the inhibitory effects of three azole antifungals (ketoconazole, voriconazole, and fluconazole) on testosterone metabolism by recombinant CYP3A4 genetic variants (CYP3A4.1 (WT), CYP3A4.2, CYP3A4.7, CYP3A4.16, and CYP3A4.18) and compared them with those previously reported for itraconazole. Testosterone 150-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 189-195 33826998-4 2021 In the present quantitative study, we investigated the inhibitory effects of three azole antifungals (ketoconazole, voriconazole, and fluconazole) on testosterone metabolism by recombinant CYP3A4 genetic variants (CYP3A4.1 (WT), CYP3A4.2, CYP3A4.7, CYP3A4.16, and CYP3A4.18) and compared them with those previously reported for itraconazole. Testosterone 150-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 214-220 33826998-4 2021 In the present quantitative study, we investigated the inhibitory effects of three azole antifungals (ketoconazole, voriconazole, and fluconazole) on testosterone metabolism by recombinant CYP3A4 genetic variants (CYP3A4.1 (WT), CYP3A4.2, CYP3A4.7, CYP3A4.16, and CYP3A4.18) and compared them with those previously reported for itraconazole. Testosterone 150-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 214-220 33384383-0 2021 Functional characterization of 40 CYP3A4 variants by assessing midazolam 1"-hydroxylation and testosterone 6beta-hydroxylation. Testosterone 94-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 32682830-12 2020 While in male, during the intrauterine period, activated AR by testosterone secretion from developing testes represses MCT-induced PXR activation and CYP3A induction, which may partially protect male fetus from MCT-induced hepatotoxicity. Testosterone 63-75 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 150-155 33105851-11 2020 Phloretin was a potent inhibitor of CYP3A4-catalyzed testosterone 6beta-hydroxylation activity. Testosterone 53-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 33933755-0 2021 Innovative C2-symmetric testosterone and androstenedione dimers: Design, synthesis, biological evaluation on prostate cancer cell lines and binding study to recombinant CYP3A4. Testosterone 24-36 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 169-175 33384383-3 2021 In this study, we characterized wild-type CYP3A4 and 40 CYP3A4 variants, including 11 new variants, detected among 4,776 Japanese individuals by assessing CYP3A4 enzymatic activities for two representative substrates (midazolam and testosterone). Testosterone 232-244 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 33384383-3 2021 In this study, we characterized wild-type CYP3A4 and 40 CYP3A4 variants, including 11 new variants, detected among 4,776 Japanese individuals by assessing CYP3A4 enzymatic activities for two representative substrates (midazolam and testosterone). Testosterone 232-244 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 33384383-5 2021 The kinetic parameters of midazolam and testosterone hydroxylation by wild-type CYP3A4 and 29 CYP3A4 variants (Km , kcat , and catalytic efficiency) were determined, and the causes of their kinetic differences were evaluated by three-dimensional structural modeling. Testosterone 40-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 80-86 33384383-5 2021 The kinetic parameters of midazolam and testosterone hydroxylation by wild-type CYP3A4 and 29 CYP3A4 variants (Km , kcat , and catalytic efficiency) were determined, and the causes of their kinetic differences were evaluated by three-dimensional structural modeling. Testosterone 40-52 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 94-100 33790108-2 2021 Hydroxylation activities of progesterone and testosterone by CYP3A4, CYP3A5, and CYP3A7 were estimated using HPLC. Testosterone 45-57 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 32049373-4 2020 Herein, we use a multi-scale modeling approach to investigate the selectivity of testosterone (TES) and dihydrotestosterone (DHT) hydroxylation catalyzed by two important P450s, CYP3A4 and CYP19A1. Testosterone 81-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-184 32049373-4 2020 Herein, we use a multi-scale modeling approach to investigate the selectivity of testosterone (TES) and dihydrotestosterone (DHT) hydroxylation catalyzed by two important P450s, CYP3A4 and CYP19A1. Testosterone 95-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 178-184 32049373-5 2020 For CYP3A4, two distinct binding modes for TES/DHT were predicted by dockings and molecular dynamics simulations, in which the experimentally identified sites of metabolism of TES/DHT can access to the catalytic center. Testosterone 43-46 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 32049373-5 2020 For CYP3A4, two distinct binding modes for TES/DHT were predicted by dockings and molecular dynamics simulations, in which the experimentally identified sites of metabolism of TES/DHT can access to the catalytic center. Testosterone 176-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 32049373-9 2020 Our study unravels the mechanism underlying the selectivity of TES/DHT hydroxylation mediated by CYP3A4 and CYP19A1 and is helpful for understanding the selectivity of other substrates that are hydroxylated by P450s. Testosterone 63-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 31755290-3 2019 To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. Testosterone 54-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 32001245-7 2020 However, progesterone inhibited testosterone 6beta-hydroxylation mediated by CYP3A4, CYP3A5, and CYP3A7. Testosterone 32-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 32001245-1 2020 Hydroxylation activity at the 6beta-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (CYP) 3A4, polymorphic CYP3A5, and fetal CYP3A7 were compared to understand the catalytic properties of the major forms of human CYP3A subfamily. Testosterone 66-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-143 32001245-2 2020 Testosterone, progesterone, and cortisol 6beta-hydroxylation activities of recombinant CYP3A4, CYP3A5, and CYP3A7 were determined by liquid chromatography. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 32001245-5 2020 A decrease in Km values for progesterone 6beta-hydroxylation by CYP3A4, CYP3A5, and CYP3A7 in the presence of testosterone was observed, and the kcat values for CYP3A5 gradually increased with increasing testosterone. Testosterone 110-122 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 32001245-5 2020 A decrease in Km values for progesterone 6beta-hydroxylation by CYP3A4, CYP3A5, and CYP3A7 in the presence of testosterone was observed, and the kcat values for CYP3A5 gradually increased with increasing testosterone. Testosterone 204-216 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 31755290-3 2019 To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. Testosterone 68-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 17-23 31108125-9 2019 Testosterone 2beta-hydroxylation was diminished in CYP3A94217Asn and CYP3A95392Thr. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-56 31108125-9 2019 Testosterone 2beta-hydroxylation was diminished in CYP3A94217Asn and CYP3A95392Thr. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-74 30301254-5 2018 6beta-hydroxylation of testosterone was used as marker reaction of CYP3A4 activity. Testosterone 23-35 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 31339834-2 2019 METHODS: Testosterone, progesterone, and cortisol 6beta-hydroxylation activities of recombinant CYP3A4 and CYP3A5 were determined by liquid chromatography. Testosterone 9-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 31339834-4 2019 RESULTS: Michaelis constants (Km) for CYP3A5- mediated 6beta-hydroxylation of testosterone and progesterone were approximately twice those for CYP3A4, whereas the value for cortisol 6beta-hydroxylation mediated by CYP3A5 was similar to the value for that by CYP3A4. Testosterone 78-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 31339834-4 2019 RESULTS: Michaelis constants (Km) for CYP3A5- mediated 6beta-hydroxylation of testosterone and progesterone were approximately twice those for CYP3A4, whereas the value for cortisol 6beta-hydroxylation mediated by CYP3A5 was similar to the value for that by CYP3A4. Testosterone 78-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 258-264 29320899-6 2019 All ITZ diastereoisomers dose-dependently inhibited CYP3A activity in both used assays, midazolam and testosterone hydroxylation. Testosterone 102-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-57 30125880-5 2018 At the pore diameter of about 65 nm, CYP3A4 shows the highest affinity to testosterone with the Michaelis-Menten constant (Kmapp) of 110.70 +- 18 muM and the relatively higher reaction rate with the Imax value of 11.85 +- 1.20 nA, which is due to the maintained native configuration and larger amount of immobilized enzyme. Testosterone 74-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-43 30125880-6 2018 Furthermore, the constructed CYP3A4/PNGF-1 nanoreactor is successfully applied to the metabolism of three steroid hormones (testosterone, estrone and progesterone), and the order of the calculated Kmapp values is consistent with literature. Testosterone 124-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 30488748-8 2019 Time dependent CYP3A4/5 inhibition was noted for testosterone and midazolam with IC50 shift of 10.9- and 39.9-fold, respectively. Testosterone 49-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 15-21 31301485-8 2019 Besides absorption, intestinal wall metabolism of testosterone (CYP3A4) was determined by showing a linear formation (R2 = 0.99; up to 165 min) of the main metabolites androstenedione and 6Beta-hydroxytestosterone, indicating no loss of metabolic capacity of the intestinal tissue within the system. Testosterone 50-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-70 30517006-0 2019 CYP3A4/5 Activity Probed with Testosterone and Midazolam: Correlation between Two Substrates at the Microsomal and Enzyme Levels. Testosterone 30-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-8 30517006-1 2019 Testosterone (TST) and midazolam (MDZ) are widely used as probes to detect CYP3A4/5 activity, but the data acquired with these two substrates do not correlate well at the microsomal level (per milligram of microsomal protein), and the reason is unclear. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-83 31339834-1 2019 PURPOSE: Hydroxylation activity at the 6beta-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (P450 or CYP) 3A4 and CYP3A5 and their molecular docking energy values were compared to understand the catalytic properties of the major forms of human CYP3A, namely, CYP3A4 and CYP3A5. Testosterone 75-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 165-170 31339834-1 2019 PURPOSE: Hydroxylation activity at the 6beta-position of steroid hormones (testosterone, progesterone, and cortisol) by human cytochromes P450 (P450 or CYP) 3A4 and CYP3A5 and their molecular docking energy values were compared to understand the catalytic properties of the major forms of human CYP3A, namely, CYP3A4 and CYP3A5. Testosterone 75-87 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 310-316 29958895-6 2018 Recently, we demonstrated that steroid bioconjugation at the allosteric site results in an increase in activity of CYP3A4 toward testosterone and 7-benzyloxy-4-trifluoromethylcoumarin oxidation. Testosterone 129-141 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 29958895-7 2018 Here, using the established bioconjugation methodology, we show how steroid bioconjugation at the allosteric site affects the heme spin state, the binding affinity (KS) of CYP3A4 for testosterone, as well as the enzyme coupling efficiency. Testosterone 183-195 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 172-178 29719052-6 2018 Testosterone 6beta-hydroxylation and midazolam 1"-hydroxylation, which are catalysed by both CYP3A4 and CYP3A5 in liver microsomes, were decreased by 25% and 45%, respectively, in the presence of 0.1 mg/ml SO-SWCNT. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 217-229 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 542-548 29382727-3 2018 Testosterone (TST) hydroxylation is the prototypical CYP3A4 reaction, displaying positive homotropic cooperativity with three binding sites. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 28986474-0 2017 Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7. Testosterone 26-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-25 29155491-7 2018 Ketoconazole effectively inhibited CLZ metabolism in five of seven livers that catalysed CYP3A4-dependent testosterone 6beta-hydroxylation at or above the median rate and in four other livers with lower intrinsic CYP3A4 activity. Testosterone 106-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 28986474-0 2017 Digging Deeper into CYP3A Testosterone Metabolism: Kinetic, Regioselectivity, and Stereoselectivity Differences between CYP3A4/5 and CYP3A7. Testosterone 26-38 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 217-229 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 3-9 28986474-1 2017 The metabolism of testosterone to 6beta-hydroxytestosterone (6beta-OH-T) is a commonly used assay to evaluate human CYP3A enzyme activities. Testosterone 18-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-121 28986474-7 2017 In silico docking studies revealed at least two different binding modes for testosterone between CYP3A4 and CYP3A7. Testosterone 76-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 64-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 3-9 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 64-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 542-548 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 217-229 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 3-9 28986474-8 2017 In CYP3A4, the most energetically favorable docking mode places testosterone in a position with the methyl groups directed toward the heme iron, which is more favorable for oxidation at C6beta, whereas for CYP3A7 the testosterone methyl groups are positioned away from the heme, which is more favorable for an oxidation event at C2alpha In conclusion, our data indicate an alternative binding mode for testosterone in CYP3A7 that favors the 2alpha-hydroxylation, suggesting significant structural differences in its active site compared with CYP3A4/5. Testosterone 217-229 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 542-548 28238727-4 2017 Testosterone, the standard compound for characterization of the human CYP3A4, was used to characterize the newly expressed equine CYPs. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-76 28944677-9 2017 A strong correlation was found between CYP3A4 and CYP3A5 abundance and activity determined using midazolam and testosterone (r > 0.600, p < 0.001). Testosterone 111-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 28344076-6 2017 While inhibition of GC towards CYP3A5 was weaker than CYP3A4 when using testosterone as substrate. Testosterone 72-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 54-60 26223917-5 2015 The enzymatic activity of CYP3A4 was measured using erythromycin and testosterone as probe substrates. Testosterone 69-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 27794450-6 2017 We further showed that hepatospheroids convert phenacetin (by CYP1A2) and testosterone (by CYP3A4) to their human-specific metabolites acetaminophen and 6beta-hydroxytestosterone with a predictive clearance rate of 0.011ml/h/106 cells and 0.021ml/h/106 cells respectively, according to first-order kinetics. Testosterone 74-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 27110874-5 2016 CYP isoenzyme activities were determined using the CYP-specific reactions, 7-ethoxycoumarin O-deethylation (CYP1A2) and testosterone 6beta-hydroxylation (CYP3A4). Testosterone 120-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-160 26899743-2 2016 Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6beta-hydroxy testosterone was noted. Testosterone 79-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 26490246-8 2016 Testosterone protected both CYP3A4 and CYP3A5 from inactivation by dronedarone and NDBD. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 28-34 27934636-7 2017 Only using the RAF derived from testosterone for CYP3A4 produced the expected CYP2C9 contribution of 72%-87% and 47%-69% for metabolism of losartan and meloxicam, respectively. Testosterone 32-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 27323294-1 2016 Cytochrome P450 (P450) 3A (CYP3A) is an enzyme responsible for the metabolism of therapeutic drugs such as midazolam, nifedipine, testosterone and triazolam. Testosterone 130-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-32 27323294-8 2016 It involves the employment of a CYP3A substrate cocktail (including midazolam, testosterone and nifedipine). Testosterone 79-91 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 27323294-9 2016 The concentration of each CYP3A probe substrate in vitro was optimized (0.1 mum for midazolam, 2 mum for testosterone and 2 mum for nifedipine) to minimize mutual drug interactions among probe substrates. Testosterone 105-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-31 26774838-0 2016 The use of isomeric testosterone dimers to explore allosteric effects in substrate binding to cytochrome P450 CYP3A4. Testosterone 20-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 26774838-3 2016 In order to better understand structural and functional aspects of binding of multiple substrate molecules to CYP3A4 we used resonance Raman and UV-VIS spectroscopy to document the effects of binding of synthetic testosterone dimers of different configurations, cis-TST2 and trans-TST2. Testosterone 213-225 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 26409144-4 2015 Multiplex experiments using the highly specific CYP2A6 with its corresponding substrate coumarin as well as the highly promiscuous CYP3A4 with testosterone were conducted. Testosterone 143-155 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-137 26296860-6 2015 Investigation of inhibitory potency towards 6 CYP isoforms generally revealed low inhibitory potency, but in the case of CYP3A4, a substrate dependent inhibition was noted using testosterone as substrate (IC50: 12.5muM). Testosterone 178-190 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-127 25892190-10 2015 The CYP3cide and ketoconazole inhibition, and testosterone and midazolam reduction of Luciferin-IPA metabolism in minipig liver microsomes substantiate that Luciferin-IPA is metabolized by CYP3A in minipigs. Testosterone 46-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 189-194 27022466-6 2015 In addition, the correlation between miR-27b and CYP3A activity, measured by dextromethorphan N-demethylation and 6beta-hydroxylation of testosterone and the gene expression of CYP3A4, VDR and PPAR alpha were assessed in 20 human liver samples. Testosterone 137-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-54 26070839-4 2015 The results indicated Bama minipigs and human CYP3A enzymes showed similar metabolic kinetics and metabolite profiles using testosterone, midazolam, and nifedipine as substrates. Testosterone 124-136 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-51 25678418-3 2015 6beta-Hydroxylation of many steroids, including cortisol, cortisone, progesterone and testosterone, was catalyzed primarily by CYP3A4. Testosterone 86-98 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-133 26350737-7 2015 Cytochrome b5mc was shown to be capable of stimulating the electrocatalytic activity of CYP3A4 in the presence of its substrate testosterone. Testosterone 128-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 25640685-2 2015 Phenacetin, dextromethorphan and testosterone, respectively, were used as CYP1A2, CYP2D6 and CYP3A4 substrates, and their metabolites were determined by validated HPLC methodologies. Testosterone 33-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 25322914-3 2015 The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. Testosterone 109-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 25457200-11 2015 HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. Testosterone 38-50 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-57 25189890-6 2014 Cytochrome P-450 (CYP)3A4 activity was measured by beta-hydroxylation of testosterone using human recombinant CYP3A4. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-25 25727956-6 2015 This effect has been confirmed with two CYP3A4 substrates, testosterone (formation of 6beta-hydroxytestosterone) and diazepam (temazepam formation). Testosterone 59-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 40-46 25145883-4 2015 HR strongly inhibited CYP1A2 and moderately inhibited CYP2C19, CYP2D6, and CYP3A4 (testosterone) but not CYP2A6, CYP2B6, CYP2C8, CYP2C9, and CYP3A4 (midazolam). Testosterone 83-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 25619394-5 2015 The metabolism of testosterone (TEST, 10 mumol/L) and dextromethorphan (DEM, 1 mumol/L), the two typical substrates for CYP3A4 and CYP2D6, in the cells was examined in the presence of different agents. Testosterone 18-30 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-126 25343516-7 2014 Catalytic activity of CYP3A4/5 towards two prototypic substrates of CYP3A enzymes, testosterone and midazolam, was determined in presence of both (+)-ketoconazole and (-)-ketoconazole in human liver microsomes. Testosterone 83-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-28 25343516-7 2014 Catalytic activity of CYP3A4/5 towards two prototypic substrates of CYP3A enzymes, testosterone and midazolam, was determined in presence of both (+)-ketoconazole and (-)-ketoconazole in human liver microsomes. Testosterone 83-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-27 24924803-1 2014 Levels of enzymes that determine testosterone catabolism such as CYP3A4 have been associated with prostate cancer (PCa) risk. Testosterone 33-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 24242708-9 2014 Mass spectrometry revealed that overexpression of CYP3A protein in prostate cancer cells resulted in a significant increase in the oxidative inactivation of testosterone and DHEA to their 6-beta-hydroxy-testosterone and 16-alpha-hydroxy-DHEA metabolites, respectively. Testosterone 157-169 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-55 24788541-8 2014 Testosterone, a CYP3A4-specific substrate, was used for detecting the metabolism activity of CYP3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 16-22 24788541-8 2014 Testosterone, a CYP3A4-specific substrate, was used for detecting the metabolism activity of CYP3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 93-99 22326629-7 2012 A HPLC assay confirmed the catalytic activity of displayed CYP3A4, using testosterone as a substrate. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-65 24749245-7 2014 Cytochrome b5mc was shown to be capable of stimulating the electrocatalytic activity of CYP3A4 to testosterone. Testosterone 98-110 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 24027778-3 2013 Direct electron transfer (DET) between CYP3A4 and CNFs was observed at a formal potential of -0.302 V. The electrocatalytic reduction current increased with the addition of drugs including testosterone and quinidine. Testosterone 189-201 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-45 23665933-5 2013 Liver microsomes genotyped as CYP3A4*1/*22 (n = 4) showed significantly lower CYP3A-dependent dextromethorphan N-demethylation, midazolam 1"-hydroxylation, and testosterone 6beta-hydroxylation activities, as well as lower expression levels of CYP3A protein (28% of control), compared with those of the CYP3A4*1/*1 group (n = 19). Testosterone 160-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 23665933-5 2013 Liver microsomes genotyped as CYP3A4*1/*22 (n = 4) showed significantly lower CYP3A-dependent dextromethorphan N-demethylation, midazolam 1"-hydroxylation, and testosterone 6beta-hydroxylation activities, as well as lower expression levels of CYP3A protein (28% of control), compared with those of the CYP3A4*1/*1 group (n = 19). Testosterone 160-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-35 23665933-5 2013 Liver microsomes genotyped as CYP3A4*1/*22 (n = 4) showed significantly lower CYP3A-dependent dextromethorphan N-demethylation, midazolam 1"-hydroxylation, and testosterone 6beta-hydroxylation activities, as well as lower expression levels of CYP3A protein (28% of control), compared with those of the CYP3A4*1/*1 group (n = 19). Testosterone 160-172 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 22939842-1 2012 We investigated the capacity for vitamin D receptor (VDR) to modulate the expression of CYP3A4 and other genes that may facilitate the oxidative inactivation of androgens such as testosterone and androstanediol within prostate cells. Testosterone 179-191 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 88-94 21372830-6 2011 Inhibition of CYP3A by erlotinib was substrate-dependent: the IC(50) values for inhibiting testosterone 6beta-hydroxylation and nifedipine metabolism were 31.3+-8.0 and 20.5+-5.3 mumol/L, respectively. Testosterone 91-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 22305191-4 2012 PSP (1.25-20muM) dose-dependently decreased CYP1A2-mediated metabolism of phenacetin to paracetamol (IC(50) 19.7muM) and CYP3A4-mediated metabolism of testosterone to 6beta-hydroxytestosterone (IC(20) 7.06muM). Testosterone 151-163 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-127 22298448-3 2012 The enzymatic activity of CYP3A4 was estimated by determing the 6beta-hydroxytestosterone metabolized from testosterone performed on a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Testosterone 77-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 22001938-5 2011 Enzyme activities were examined using high performance liquid chromatography (HPLC) assays with probe substrates dextromethorphan and testosterone for CYP2D6 and CYP3A4, respectively. Testosterone 134-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 162-168 21722087-8 2011 The use of luciferin-IPA allows CYP3A4 activity to be quantified rapidly using a plate reader, thereby avoiding the need for LC/MS that is required for traditional substrates such as testosterone and midazolam. Testosterone 183-195 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 19921206-1 2011 PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. Testosterone 207-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 187-193 21372830-7 2011 Erlotinib also exhibited the time-dependent inhibition on CYP3A, regardless of the probe substrate used: the value of K(I) and k(inact) were 6.3 mumol/L and 0.035 min(-1) for midazolam; 9.0 mumol/L and 0.045 min(-1) for testosterone; and 10.1 mumol/L and 0.058 min(-1) for nifedipine. Testosterone 220-232 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-63 22523293-5 2012 Cytochrome P-450 (CYP)3A4 activity was measured by beta-hydroxylation of testosterone in human recombinant CYP3A4. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-25 22523293-5 2012 Cytochrome P-450 (CYP)3A4 activity was measured by beta-hydroxylation of testosterone in human recombinant CYP3A4. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 22351667-5 2012 Cytochrome P-450 (CYP)3A4 activity was measured by beta-hydroxylation of testosterone in human recombinant CYP3A4. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-25 22351667-5 2012 Cytochrome P-450 (CYP)3A4 activity was measured by beta-hydroxylation of testosterone in human recombinant CYP3A4. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 21842479-2 2012 Recombinant human CYP3A4 and CYP2D6 enzymes were used and the activities were expressed by the metabolism of testosterone and dextromethorphan with ketoconazole and quinidine as positive inhibitor controls, respectively. Testosterone 109-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 22719896-4 2012 Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ~70% of wild-type activity by Y181D and A287P mutations. Testosterone 97-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 22001672-6 2011 However, potent inhibition of CYP3A4 by limonin is observed with IC50 values of 6.20 muM (CYP3A4/testosterone) and 19.10 muM (CYP3A4/midazolam). Testosterone 97-109 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 20977456-8 2010 KEY RESULTS: N-desmethylimatinib formation was correlated with microsomal oxidation of the CYP3A4 substrates testosterone (rho= 0.60; P < 0.01) and midazolam (rho= 0.46; P < 0.05), and the CYP2C8 substrate paclitaxel (rho= 0.58; P < 0.01). Testosterone 109-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 91-97 21207936-2 2011 Resonance Raman (RR) spectroscopy is used to help define active site structural responses of nanodisc-incorporated CYP3A4 to the binding of three substrates: bromocriptine (BC), erythromycin (ERY), and testosterone (TST). Testosterone 202-214 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 21207936-2 2011 Resonance Raman (RR) spectroscopy is used to help define active site structural responses of nanodisc-incorporated CYP3A4 to the binding of three substrates: bromocriptine (BC), erythromycin (ERY), and testosterone (TST). Testosterone 216-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 115-121 21177853-0 2011 Analysis of heterotropic cooperativity in cytochrome P450 3A4 using alpha-naphthoflavone and testosterone. Testosterone 93-105 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 42-61 21177853-1 2011 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of the substrates it metabolizes, including testosterone (TST) and alpha-naphthoflavone (ANF). Testosterone 121-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 21177853-1 2011 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of the substrates it metabolizes, including testosterone (TST) and alpha-naphthoflavone (ANF). Testosterone 121-133 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 21177853-1 2011 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of the substrates it metabolizes, including testosterone (TST) and alpha-naphthoflavone (ANF). Testosterone 135-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 21177853-1 2011 Cytochrome P450 3A4 (CYP3A4) displays non-Michaelis-Menten kinetics for many of the substrates it metabolizes, including testosterone (TST) and alpha-naphthoflavone (ANF). Testosterone 135-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 20879989-2 2010 In the purified proteoliposomes, CYP3A4 binds testosterone with Kd (app)=36+-6 muM and Hill coefficient=1.5+-0.3, and 75+-4% of the CYP3A4 can be reduced by NADPH in the presence of testosterone. Testosterone 46-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 20879989-2 2010 In the purified proteoliposomes, CYP3A4 binds testosterone with Kd (app)=36+-6 muM and Hill coefficient=1.5+-0.3, and 75+-4% of the CYP3A4 can be reduced by NADPH in the presence of testosterone. Testosterone 46-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 132-138 20879989-2 2010 In the purified proteoliposomes, CYP3A4 binds testosterone with Kd (app)=36+-6 muM and Hill coefficient=1.5+-0.3, and 75+-4% of the CYP3A4 can be reduced by NADPH in the presence of testosterone. Testosterone 182-194 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 33-39 20818746-10 2010 The rate of testosterone 6beta-hydroxylation, a measure of CYP3A function inside BALs, increased 4-fold in cBAL119 BALs versus HepG2 BALs. Testosterone 12-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 59-64 20937004-5 2010 AZD2624 exhibited an inhibitory effect on microsomal CYP3A4/5 activities with apparent IC(50) values of 7.1 and 19.8 microM for midazolam and testosterone assays, respectively. Testosterone 142-154 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 20624855-6 2010 Testosterone protected CYP3A4 from inactivation by lapatinib. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 20697309-7 2010 The A503 V polymorphism reduced the CYP3A4 activity to 61-77% of WT with testosterone and midazolam, but had nearly WT activity with quinidine and erythromycin. Testosterone 73-85 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-42 20699409-3 2010 Thin-layer (TL) Matrigel was found to yield the highest basal and induced levels of CYP3A activity as determined by testosterone 6beta-hydroxylation. Testosterone 116-128 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-89 20203109-3 2010 In response to studies that suggested the presence of several binding regions within the CYP3A4 active site, multiple probe substrates are often used for in vitro CYP3A4 DDI studies, including midazolam (the clinical standard), felodipine/nifedipine, and testosterone. Testosterone 255-267 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 20233841-5 2010 By using the CYP3A4-specific substrates luciferin 6" benzyl ether, testosterone, and midazolam, we could confirm that the increased CYP3A4 gene expression also was accompanied by a similar increase in catalytic activity, inhibitable by the CYP3A4-selective inhibitor ketoconazole. Testosterone 67-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 20233841-5 2010 By using the CYP3A4-specific substrates luciferin 6" benzyl ether, testosterone, and midazolam, we could confirm that the increased CYP3A4 gene expression also was accompanied by a similar increase in catalytic activity, inhibitable by the CYP3A4-selective inhibitor ketoconazole. Testosterone 67-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 132-138 20233841-5 2010 By using the CYP3A4-specific substrates luciferin 6" benzyl ether, testosterone, and midazolam, we could confirm that the increased CYP3A4 gene expression also was accompanied by a similar increase in catalytic activity, inhibitable by the CYP3A4-selective inhibitor ketoconazole. Testosterone 67-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 132-138 20203109-9 2010 Finally, Simcyp was used to predict the in vivo magnitude of CYP3A4 DDIs caused by AMG 458 using midazolam, sildenafil, simvastatin, and testosterone as probe substrates. Testosterone 137-149 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 19414624-5 2009 Marked increase in 6beta-hydroxylation of testosterone by CYP3A4 was also observed in the 6-day 1,25(OH)(2)D(3)-treated (100 nM) cell lysate. Testosterone 42-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 19480428-1 2009 Testosterone hydroxylation is a prototypical reaction of human cytochrome P450 3A4, which metabolizes about 50% of oral drugs on the market. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-82 19490052-6 2009 RESULTS: In both, humans and cell lines, the expression of testosterone metabolising CYP3A4 (human) or CYP3A11 (mouse) and AR was up-regulated when P450-inducing AEDs and/or prednisolone had been applied. Testosterone 59-71 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 85-91 19020497-4 2009 In vitro functional analyses indicate that CYP3A4*18 is a gain-of-function mutation in sex steroid metabolism, resulting in rapid oxidation of estrogens and testosterone; in vivo pharmacokinetics using midazolam (MDZ) verify the altered activity of the CYP3A4*18, showing lower metabolic turnover in the mutant than in the wild type. Testosterone 157-169 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 21218106-4 2008 The aim of this study was to evaluate the efficiency of different in vitro systems containing individual enzymes of the mixed-function monooxygenase system to oxidize two model substrates of CYP3A enzymes, exogenous and endogenous compounds, alpha-naphtoflavone (alpha-NF) and testosterone, respectively. Testosterone 277-289 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 191-196 18647599-7 2008 Flutamide and haloperidol were further demonstrated to cause CYP3A4 induction in human cryopreserved hepatocytes based on testosterone 6beta-hydroxylation activity. Testosterone 122-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 18803184-1 2008 An electrophoretically mediated microanalysis method for the determination of CYP3A4 activity using testosterone and nifedipine as substrates was developed. Testosterone 100-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 18803184-7 2008 Using the Lineweaver-Burk equation, the Michaelis constants (K(m)) for the oxidation of testosterone and nifedipine by CYP3A4 were calculated to be 58.6+/-8.3 and 19.1+/-2.4 microM, respectively, which are consistent with off-line assay and previously reported values. Testosterone 88-100 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 119-125 18431572-8 2008 In human liver microsomal preparations, eribulin suppressed the activities of CYP3A4-mediated testosterone and midazolam hydroxylation with an apparent K (i) of approximately 20 microM. Testosterone 94-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 21218106-7 2008 The results presented in this study demonstrate the suitability of the supersomal CYP3A4 systems for studies investigating oxidation of testosterone and alpha-NF in vitro. Testosterone 136-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-88 18819885-3 2008 After 15 min of culture, the substrates (testosterone for CYP3A4 and phenacetin for CYP1A2) were added and incubated for another 20 min. Testosterone 41-53 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-64 18395506-7 2008 In addition, the red spectral component, with an apparent K(D)=2.2muM, is selectively eliminated by titration with the known allosteric effectors of CYP3A4, alpha-napthoflavone and testosterone. Testosterone 181-193 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 149-155 17826359-6 2008 Using erythromycin and testosterone as substrates, we demonstrated that CYP3A catalysis exhibited non-Michaelis-Menten kinetics in GCL cells, and that V(max)/K(m) values were significantly increased due to rifampicin-treatment. Testosterone 23-35 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-77 18322939-11 2008 Fipronil can inhibit testosterone metabolism by CYP3A4 and is an effective inducer of CYP isoforms in human hepatocytes. Testosterone 21-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 48-54 18328680-8 2008 Enzyme activity of CYP3A4, measured by testosterone metabolism, was increased after 24h by RIF. Testosterone 39-51 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 19-25 18380401-3 2008 Initial velocity of testosterone 6beta-oxidation using human liver microsomes was determined as an indicator of the CYP3A activities. Testosterone 20-32 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-121 17650504-3 2007 To understand the overall kinetic processes operating in CYP3A4, we documented the kinetics of autoxidation of the oxy-ferrous intermediate of CYP3A4 as a function of testosterone concentration. Testosterone 167-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 19326769-5 2008 Chlorpyrifos and DEET also mediated the expression of CYP isoforms, particularly CYP3A4, CYP2B6 and CYP1A1, as shown by CYP3A4-specific protein expression, testosterone metabolism and CYP1Al-specific activity assays. Testosterone 156-168 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 17650504-3 2007 To understand the overall kinetic processes operating in CYP3A4, we documented the kinetics of autoxidation of the oxy-ferrous intermediate of CYP3A4 as a function of testosterone concentration. Testosterone 167-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-149 17650504-6 2007 In contrast, the slow phase in the kinetics of cyanide binding to the ferric CYP3A4 correlated with a shift of the heme iron spin state, which is only caused by the association of a second molecule of testosterone. Testosterone 201-213 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 17526062-4 2007 We show that CYP3A4 tolerates only small amounts (<15 %) of water-miscible organic cosolvents or ionic liquids before its activity toward testosterone drops below detection. Testosterone 141-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 17914095-2 2007 Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. Testosterone 47-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-18 17914095-2 2007 Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. Testosterone 47-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 20-25 17914095-2 2007 Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. Testosterone 47-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 168-173 17526062-6 2007 CYP3A4 activity in the absence of buffer was only >or=10 % in solvents of the alkane series, with a minimum of 0.85 % water, and with the addition of sucrose and testosterone before enzyme lyophilization. Testosterone 165-177 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 17392390-6 2007 In the assay, three compounds (midazolam, nifedipine, and testosterone) were compared as CYP3A probe substrates. Testosterone 58-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-94 17555301-7 2007 Surprisingly, at high concentrations of allosteric substrates, the amplitude of the spin shift in both CYP3A4 in solution and Nanodiscs was very low, demonstrating that hydrostatic pressure induces neither substrate dissociation nor an increase in the heme pocket hydration in the complexes of the pressure-promoted conformation of CYP3A4 with 1-PB or testosterone. Testosterone 352-364 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 103-109 17555301-8 2007 These findings suggest that the mechanisms of interactions of CYP3A4 with 1-PB and testosterone involve an effector-induced transition that displaces a system of conformational equilibria in the enzyme toward the state(s) with decreased solvent accessibility of the active site so that the flux of water into the heme pocket is impeded and the high-spin state of the heme iron is stabilized. Testosterone 83-95 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 17459328-0 2007 Energetics of heterotropic cooperativity between alpha-naphthoflavone and testosterone binding to CYP3A4. Testosterone 74-86 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 98-104 17459328-2 2007 Heterotropic cooperativity of drug binding to CYP3A4 was examined with the flavanoid, alpha-naphthoflavone (ANF) and the steroid, testosterone (TST). Testosterone 130-142 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 17213193-3 2007 CYP3A4 in this complex showed a nearly complete conversion from the low- to high-spin state when saturated with testosterone (TS) and no noticeable modulation due to the presence of cytochrome P450 reductase. Testosterone 112-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 17357170-2 2007 These compounds are unique inhibitors of cytochrome P450 3A4 (CYP3A4) and display similar IC(50) values in the microM range for the CYP3A4 substrates midazolam, testosterone, and nifedipine. Testosterone 161-173 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-60 17084830-7 2006 Similar increases and decreases were observed in CYP3A4-specific activity levels as measured using 6beta-hydroxytestosterone formation following incubation with testosterone. Testosterone 112-124 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 17368239-5 2007 CYP3A activity was quantified from liver microsomes by using testosterone as a probe, and hepatic steatosis was defined to be present if >5% of hepatocytes had large globules of intracellular fat displacing the nucleus. Testosterone 61-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 16762915-6 2006 In substrate-free CYP3A4, the oxy complex is extremely unstable with a half-life of approximately 30 ms at 5 degrees C. Saturation with testosterone or bromocriptine stabilizes the oxy-ferrous intermediate. Testosterone 136-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 16481174-3 2006 Compounds were designed, synthesised and tested for their ability to inhibit CYP3A4 activity in human liver microsomes using testosterone as the marker substrate. Testosterone 125-137 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 16941956-6 2006 Our results suggest that liver microsomes from Chinese Bama miniature pigs are similar to those from humans in regard to metabolism of nifedipine and testosterone (both are probe substrates for human CYP3A4). Testosterone 150-162 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 200-206 16713641-2 2006 CYP3A plays a broad role in biotransforming both exogenous compounds and endogenous hormones such as testosterone and estradiol. Testosterone 101-113 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 16443667-7 2006 There was a high correlation between the formation of M1, determined in 10 human liver microsomal samples, and 6beta-hydroxylation of testosterone catalyzed by CYP3A4/5 (r = 0.93). Testosterone 134-146 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-166 16501008-9 2006 The K(i) values for CYP2C9 and CYP2C19 were 1.7 and 3.3 microM, respectively, and those for CYP3A4 were 8.3 and 2.9 microM, using two substrates, testosterone and midazolam, respectively. Testosterone 146-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-98 16434211-7 2006 The protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta-hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5 nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the parental yeast, and almost two times the activity of hCYP3A4 from homologous human liver microsome. Testosterone 92-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 22-29 16434211-7 2006 The protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta-hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5 nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the parental yeast, and almost two times the activity of hCYP3A4 from homologous human liver microsome. Testosterone 92-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-134 16434211-7 2006 The protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta-hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5 nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the parental yeast, and almost two times the activity of hCYP3A4 from homologous human liver microsome. Testosterone 92-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-134 16434211-7 2006 The protein amount of hCYP3A4 in BWG-CPR/3A4 was 35.53 pmol/mg, and the 6beta-hydroxylation testosterone formation activity of hCYP3A4 expressed was 7.5 nmol/min/nmol CYP, 30 times higher than the activity of hCYP3A4 expressed in the parental yeast, and almost two times the activity of hCYP3A4 from homologous human liver microsome. Testosterone 92-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 127-134 16771648-10 2006 Enhanced metabolizing activity of CYP3A4, measured by the amount 6beta-testosterone formed from testosterone, and that of the phase II enzyme glucuronosyltransferases (UGT) further indicated that the tissue-engineered C3A spheroids may provide an efficient experimental tool for predicting drug activities by these CYPs. Testosterone 71-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 16416302-2 2006 Our aim was to predict quantitatively the drug-drug interaction (DDI) potential of five macrolides from in vitro studies using testosterone as the CYP3A substrate, and to compare the predictions generated from human liver microsomal and recombinant CYP3A4 data. Testosterone 127-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 147-152 16416302-11 2006 CONCLUSIONS: The DDI potential of five macrolide antibiotics was quantitatively predicted from in vitro studies using testosterone as the CYP3A substrate with HLM as the enzyme source. Testosterone 118-130 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 138-143 27699667-2 2006 CYP3A enzymes from various species, including human, metabolize testosterone by a 6beta-hydroxylation reaction, which is unique to this P450 subfamily. Testosterone 64-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 16337070-7 2006 Anti-CYP3A4 antibody markedly inhibited MB(2), MB(4), and MC formation and also 6 beta-hydroxytestosterone formation from testosterone. Testosterone 94-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 5-11 16337070-8 2006 The CYP3A-dependent reaction of testosterone 6 beta-hydroxylation showed a high correlation with 4 beta-C hydroxylation of TRB (r(2)=0.97, P<0.0001), O-demethylation of TRB (r(2)=0.95, P<0.0001), and 4 beta-C hydroxylation of TRC (r(2)=0.99, P<0.0001). Testosterone 32-44 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-9 16719384-2 2006 CYP3A enzymes from various species, including human, metabolize testosterone by a 6beta-hydroxylation reaction, which is unique to this P450 subfamily. Testosterone 64-76 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-5 16719384-3 2006 A thin-layer chromatographic method is described for the determination of 6beta-hydroxytestosterone formed enzymatically by incubation of [14C]-testosterone with cDNA-expressed CYP3A enzymes or liver microsomes. Testosterone 87-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 177-182 27699667-3 2006 A thin-layer chromatographic method is described for the determination of 6beta-hydroxytestosterone formed enzymatically by incubation of [14C]-testosterone with cDNA-expressed CYP3A enzymes or liver microsomes. Testosterone 87-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 177-182 16601787-1 2005 Enzyme activities of the CYP enzymes (CYP3A4, CYP2C9 and CYP2A6) were determined using classical substrates (testosterone, diclofenac and coumarin, respectively) as well as with luminogenic or fluorogenic substrates in micromethod arrangement. Testosterone 109-121 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-44 16414488-2 2006 CYP3A4, a protein in the cytochrome P-450 supergene family, facilitates the oxidative deactivation of testosterone. Testosterone 102-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 16012074-5 2005 There was a high correlation (r>0.96) between the rate of formation of M12 and M13 and 6 beta-hydroxylation of testosterone catalysed by CYP3A4/5. Testosterone 114-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 16112913-8 2005 Incubations containing recombinant CYP3A, human NADPH-cytochrome P-450 oxidoreductase reductase, human cytochrome b5, and a NADPH generation system catalyzed the dealkylation of BFC and hydroxylation of testosterone with a high degree of stereoselectivity. Testosterone 203-215 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-40 15910734-3 2005 The addition of testosterone to the incubation mixture completely abolished the second phase to yield a typical, hyperbolic curve, presumably through the disruption in the formation of a pi-pi stacked pyrene complex within the CYP3A4 active site. Testosterone 16-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 227-233 15845858-6 2005 CYP3A4 expression was minimal based on mRNA expression (1000-fold lower than CYP3A7) and the ratio of testosterone 2alpha- (T2alphaH) to 6beta- (T6betaH) hydroxylation. Testosterone 102-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15689501-3 2005 Testosterone 6beta-hydroxylation or midazolam 1"-hydroxylation was used to quantify CYP3A activity. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 84-89 15684493-8 2005 Furthermore, oxatomide inhibited the metabolism of (+/-) bufuralol and testosterone, model substrates for CYP2D6 and CYP3A4, respectively, in a dose-dependent manner with the Ki values of 57.4 and 24.3 microM, respectively. Testosterone 71-83 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 117-123 15667229-0 2005 The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: ligand binding and spin state equilibria. Testosterone 31-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 55-74 15667229-5 2005 The CYP3A4 substrate testosterone (TST) has been shown previously by absorbance spectroscopy to induce spin state changes that are characteristic of a low spin to high spin conversion. Testosterone 21-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 15608130-0 2005 Development and validation of a high-throughput radiometric CYP3A4/5 inhibition assay using tritiated testosterone. Testosterone 102-114 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 15608130-3 2005 The assay is based on the release of tritium as tritiated water that occurs upon CYP3A4/5-mediated 6beta-hydroxylation of testosterone labeled with tritium in the 6beta position. Testosterone 122-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 81-87 15608130-7 2005 Competition experiments using tritiated and unlabeled testosterone indicated that CYP3A4/5-mediated 6beta-hydroxylation exhibits positive cooperativity and a modest kinetic isotope effect. Testosterone 54-66 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 82-88 15546903-6 2005 In characterized human liver microsomes, 24-hydroxylation of 1 alpha OHD(2) by CYP3A4 correlated significantly with 6 beta-hydroxylation of testosterone, a marker of CYP3A4 activity. Testosterone 140-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 79-85 15546903-6 2005 In characterized human liver microsomes, 24-hydroxylation of 1 alpha OHD(2) by CYP3A4 correlated significantly with 6 beta-hydroxylation of testosterone, a marker of CYP3A4 activity. Testosterone 140-152 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 166-172 15459178-6 2004 Individuals with a low expression ratio, exhibiting a large difference of transcript level between the two alleles, revealed extremely low levels of total hepatic CYP3A4 mRNA, and thus low metabolic capability as assessed by testosterone 6beta-hydroxylation. Testosterone 225-237 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 163-169 15560889-17 2004 Testosterone metabolism was activated by carbofuran in HLM and CYP3A4, however, less activation was observed for carbofuran metabolism by testosterone in HLM and CYP3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 15540736-2 2004 Cytochrome P450 3A4 (CYP3A4) oxidatively deactivates testosterone by converting it to biologically less active metabolites. Testosterone 53-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 15548719-2 2004 The enzyme products of CYP3A4 and CYP3A43 are involved in testosterone metabolism. Testosterone 58-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 23-29 15548719-11 2004 The observation that CYP3A4 and CYP3A43 were associated with prostate cancer, are not in linkage equilibrium, and are both involved in testosterone metabolism, suggest that both CYP3A4*1B and CYP3A43*3 may influence the probability of having prostate cancer and disease severity. Testosterone 135-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 15548719-11 2004 The observation that CYP3A4 and CYP3A43 were associated with prostate cancer, are not in linkage equilibrium, and are both involved in testosterone metabolism, suggest that both CYP3A4*1B and CYP3A43*3 may influence the probability of having prostate cancer and disease severity. Testosterone 135-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 15540736-2 2004 Cytochrome P450 3A4 (CYP3A4) oxidatively deactivates testosterone by converting it to biologically less active metabolites. Testosterone 53-65 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 15369821-8 2004 The purified CYP 3A4:Nanodiscs showed a heretofore undescribed high level of homotropic cooperativity in the binding of testosterone. Testosterone 120-132 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-20 15369821-9 2004 Soluble CYP 3A4:Nanodisc retains its known function and shows prototypic hydroxylation of testosterone when driven by hydrogen peroxide. Testosterone 90-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-15 15375599-7 2004 CYP3A4 protein and an intermediate metabolite of testosterone by CYP3A4 were detected in OUMS-29/H11 cells cultivated in RFB >29 days. Testosterone 49-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15373842-0 2004 Testosterone 1 beta-hydroxylation by human cytochrome P450 3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-62 15373842-1 2004 Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylation products in addition to 6 beta-hydroxytestosterone, the major product. Testosterone 50-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-25 15375599-7 2004 CYP3A4 protein and an intermediate metabolite of testosterone by CYP3A4 were detected in OUMS-29/H11 cells cultivated in RFB >29 days. Testosterone 49-61 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 15285839-2 2004 We assessed the effect of ethanol on CYP3A-mediated biotransformation using human liver microsomes in-vitro with three prototypic CYP3A-mediated reactions: nifedipine to oxidized nifedipine, triazolam to its 1-hydroxy (1-OH TRZ) and 4-hydroxy (4-OH TRZ) metabolites, and testosterone to 6beta-hydroxytestosterone (6beta-OH TST). Testosterone 271-283 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 37-42 15232676-5 2004 Of the enzymes that are capable of catalyzing 6beta-hydroxylation of testosterone (CYP3A and CYP1A1), only CYP3A4 mRNA and protein expression correlated significantly with the Vmax values (r=0.51, p<0.001 and r=0.66, p<0.001, respectively). Testosterone 69-81 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 107-113 15232676-8 2004 Together, these data suggest that the specific activities of CYP3A4 and CYP3A5 towards testosterone are comparable. Testosterone 87-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 20945304-0 2004 Human cytochrome P450: metabolism of testosterone by CYP3A4 and inhibition by ketoconazole. Testosterone 37-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 14560315-1 2004 Genes involved in the testosterone biosynthetic pathway - such as CYP17A1, CYP3A4, and SRD5A2 - represent strong candidates for affecting prostate cancer. Testosterone 22-34 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 15277015-8 2004 Typical CYP3A4 substrates, such as midazolam, testosterone, nifedipine and verapamil, are shown to fit the putative active site of the enzyme structure in a manner consistent with their known positions of metabolism. Testosterone 46-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 8-14 15621665-2 2004 6beta-hydroxytestosterone production, a marker of CYP3A4 activity, was approximately 3- and 7-fold greater in 1,25(OH)2D3-treated cells compared to untreated cells when incubated with 50 and 500 microM testosterone, respectively, and was unaffected by the addition of digoxin to reduce Pgp activity. Testosterone 13-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-56 14977870-4 2004 CYP2B6 and CYP3A4 protein and activities were assessed by Western blotting, bupropion hydroxylation, and testosterone 6beta-hydroxylation, respectively. Testosterone 105-117 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 11-17 14634046-6 2004 Testosterone (TST) inhibited 1-OH-TRZ formation and activated 4-OH-TRZ formation in all age groups, with no significant differences among the groups; this suggests that the drug-drug interaction potential using TRZ and TST as index CYP3A substrates may not change with age. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 232-237 14712470-0 2004 Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole: Testosterone and methadone as substrates. Testosterone 82-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-55 14712470-0 2004 Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole: Testosterone and methadone as substrates. Testosterone 82-94 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 57-63 14712470-6 2004 Dextro- and levo-KTZ exhibited modest enantioselective differences with respect to CYP3A4 inhibition of testosterone and methadone metabolism. Testosterone 104-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 14709627-6 2004 Inhibition of CYP3A by azamulin appeared sigmoidal and well behaved with the substrates 7-benzyloxy-4-trifluoromethylcoumarin, testosterone, and midazolam. Testosterone 127-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-19 14636322-5 2003 The rate of testosterone 6beta-hydroxylation by hepatocytes served as a marker for CYP3A4 activity. Testosterone 12-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 12814972-1 2003 Midazolam, triazolam (TRZ), testosterone, and nifedipine have all been widely used as probes for in vitro metabolism of CYP3A. Testosterone 28-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-125 12766253-10 2003 Drug-drug interaction studies for CYP3A4 using pooled human hepatic microsomes and avasimibe at various concentrations, revealed IC50 values of 20.7, 1.6, and 3.1 microM using testosterone, midazolam, and felodipine as probe substrates, respectively. Testosterone 176-188 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 14552748-4 2003 We have designed and synthesized a new fluorescent probe, a testosterone substituted at the 6beta- position with a fluorescent deazaflavine moiety which is able to inhibit to the same extent the hydroxylation of compounds known to bind to different sites in the CYP 3A4 active site. Testosterone 60-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 262-269 12920166-2 2003 A set of in vitro interaction studies was performed in human lymphoblast-expressed CYP3A4 involving representatives of two CYP3A4 subclasses, midazolam (MDZ) and testosterone (TST); a distinct subgroup, nifedipine (NIF); and its structural analog, felodipine (FEL). Testosterone 176-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 12814962-3 2003 In studies with a characterized bank of human liver microsome preparations, a good correlation (r2 = 0.932) was obtained between formation of N-desmethyl eletriptan (DETT) and CYP3A4-catalyzed testosterone 6 beta-hydroxylation. Testosterone 193-205 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 176-182 12814972-3 2003 Recombinant CYP3A4 and CYP3A5 (rCYP3A4 and rCYP3A5) both produced 1-OH and 4-OH metabolites from midazolam and triazolam, 6 beta-hydroxytestosterone from testosterone, and oxidized nifedipine from nifedipine. Testosterone 136-148 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 12814972-10 2003 Thus, CYP3A4 and CYP3A5 both contribute to midazolam, triazolam, testosterone, and nifedipine biotransformation in HLMs, with CYP3A5 being metabolically less active than CYP3A4 in general. Testosterone 65-77 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 12601364-6 2003 When testosterone, a substrate for CYP3A4, was added to the rifampicin-treated cell culture, 6 beta-hydroxy testosterone as a metabolite was formed. Testosterone 5-17 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 35-41 12893521-7 2003 Additionally, 7-benzyloxyresorufin O-debenzylation by recombinant CYP3A4 was increased by the addition of alpha-naphthoflavone, testosterone and progesterone but not by quinidine, whereas no chemicals tested could activate the O-debenzylation of 7-benzyloxyresorufin by CYP2B6. Testosterone 128-140 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 12893521-10 2003 Quinidine and testosterone increased 7-benzyloxyresorufin O-debenzylase and nifedipine oxidase activities, respectively, in human liver microsomes, whereas activation was not observed in CYP3A4. Testosterone 14-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-94 12692107-4 2003 High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Testosterone 66-78 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 14-20 12642463-0 2003 Inhibition and activation of the human liver microsomal and human cytochrome P450 3A4 metabolism of testosterone by deployment-related chemicals. Testosterone 100-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-85 11726664-9 2002 Heterologous expression of the chimeric species composed of CYP3A43 exon 1 joined to exons 2-13 of CYP3A4 revealed catalytic activity toward testosterone. Testosterone 141-153 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 60-66 12368055-1 2002 The effects of human and bovine serum proteins on CYP3A activity, using testosterone as the probe substrate, were investigated in human liver microsomes. Testosterone 72-84 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 50-55 12358527-11 2002 These changes are reversed by the CYP3A4 substrate testosterone. Testosterone 51-63 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 11950795-6 2002 Tamoxifen and 4-hydroxytamoxifen (1-10 microM) significantly increased the CYP3A4 expression and activity (measured as the rate of testosterone 6beta-hydroxylation). Testosterone 131-143 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 75-81 11956645-3 2002 CYP3A4 may influence PRCa through its role in testosterone metabolism. Testosterone 46-58 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 11936218-3 2002 Baicalein and 2",5,6",7-tetrahydroxyflavone inhibited hepatic testosterone 6beta-hydroxylation (CYP3A4) activity with a IC50 of 17.4 and 7.8 microM, respectively. Testosterone 62-74 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 96-102 15618727-0 2003 Substrate dependent inhibition profiles of fourteen drugs on CYP3A4 activity measured by a high throughput LCMS/MS method with four probe drugs, midazolam, testosterone, nifedipine and terfenadine. Testosterone 156-168 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 61-67 11717184-0 2001 Multisite kinetic models for CYP3A4: simultaneous activation and inhibition of diazepam and testosterone metabolism. Testosterone 92-104 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 29-35 11805199-5 2002 Furthermore, both epinephrine and adrenochrome were found to be inhibitors of CYP3A4-mediated oxidation of testosterone. Testosterone 107-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-84 11701226-6 2001 Testosterone, chlorzoxazone, and ethoxyresorufin were used as selective substrates for CYP3A, CYP2E1 and CYP1A1/1A2, respectively. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-92 15618664-0 2002 CYP3A4 gene polymorphisms influence testosterone 6beta-hydroxylation. Testosterone 36-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 15618664-3 2002 We measured testosterone hydroxylation in wild-type CYP3A4 and these three variants using a mammalian expression system. Testosterone 12-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 52-58 15618664-4 2002 Testosterone 6beta-, 2beta-, and 15beta-hydroxylations by the variant CYP3A4 forms T363M (<40%) and T185S (<60%) were reduced as compared with the wild-type in transient expression assays. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 70-76 11717184-3 2001 We have investigated the hypothesis that CYP3A4 may bind multiple molecules simultaneously using diazepam (DZ) and testosterone (TS). Testosterone 115-127 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 11714865-0 2001 Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. Testosterone 91-103 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 11714865-12 2001 Testosterone and the insecticide chlorpyrifos were used to assess the catalytic activities of the most common CYP3A4 allele (CYP3A4*1) and its allelic variants. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 11714865-13 2001 CYP3A4 F189S exhibited lower turnover numbers for testosterone and chlorpyrifos, while CYP3A4 L293P had higher turnover numbers for both substrates. Testosterone 50-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 10901704-6 2000 Further evidence for involvement of CYP3A P450s was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19-mediated reactions. Testosterone 179-191 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 36-41 11602524-0 2001 Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin bind to different domains within the active site of cytochrome P450 3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 131-150 11602524-1 2001 Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin, marker substrates for cytochrome P450 3A4 are commonly used within the pharmaceutical industry to screen new chemical entities as inhibitors of CYP3A4 in a high-throughput manner to predict the potential for drug-drug interactions. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-121 11602524-1 2001 Testosterone, 7-benzyloxyquinoline, and 7-benzyloxy-4-trifluoromethyl-coumarin, marker substrates for cytochrome P450 3A4 are commonly used within the pharmaceutical industry to screen new chemical entities as inhibitors of CYP3A4 in a high-throughput manner to predict the potential for drug-drug interactions. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 224-230 11640917-9 2001 In addition, time- and concentration-dependent inactivation of human CYP3A4-mediated 6beta-hydroxylation of testosterone by alpha-NF, was determined. Testosterone 108-120 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 11414684-1 2001 The inhibition of CYP3A4-mediated oxidation of triazolam and testosterone was assessed in the presence of a selection of known CYP3A4 substrates and inhibitors. Testosterone 61-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 18-24 11414684-4 2001 In additional studies, residual CYP3A4 activity toward testosterone and triazolam hydroxylation was measured after pretreatment with the CYP3A4 mechanism based inhibitor, midazolam. Testosterone 55-67 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-38 11160617-4 2001 In cultured cells, the presence of pgp increased the apparent K(m) for the 6beta-hydroxylase activity of CYP3A4 toward testosterone and cortisol by a factor of 1.7 and 4, respectively. Testosterone 119-131 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 105-111 11197065-8 2000 Further, DHEC demonstrated an inhibitory effect on CYP3A4-mediated testosterone metabolism and additionally could induce CYP3A4 and CYP2E1 mRNA when added at 10 microM to cultured human hepatocytes. Testosterone 67-79 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 51-57 11745731-7 2001 Functional studies, using the CYP3A probe testosterone, showed that CYP3A activity was completely absent only in uninduced Caco-2 cells. Testosterone 42-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 68-73 11745731-9 2001 The maximum velocity (Vmax) and the apparent Michaelis constant (Km) for the 6beta-hydroxylation of testosterone by CYP3A4 in intact Caco-2 monolayers were similar to those obtained from human intestinal microsomes. Testosterone 100-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-122 11454902-10 2001 The activity of testosterone 6beta-hydroxylation (a selective probe for CYP3A4/5 activity) strongly correlated with the rate of formation of 2-OH-E2, 4-OH-E2, and several other hydroxyestrogen metabolites by both male and female liver microsomes. Testosterone 16-28 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 72-78 12690615-4 2001 The CYP3A4 gene is associated with oxidative deactivation of testosterone. Testosterone 61-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 11458985-1 2001 Kinetics of testosterone 6beta-hydroxylation were determined using a reconstituted system that consisted of CYP3A4, cytochrome b5 and NADPH-cytochrome P450 oxidoreductase (OR) with similar ratios as those seen in human liver microsomes and compared with those determined using human liver microsomes. Testosterone 12-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 108-114 11458985-3 2001 The Km values of testosterone 6beta-hydroxylation obtained from the reconstituted systems with high and low OR/CYP3A4 ratios were 29.3 and 35.2 microM, respectively, which were similar to that of the corresponding human liver microsomal samples (23.2 and 40.0 microM, respectively). Testosterone 17-29 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 111-117 11422004-3 2001 Kinetics of CYP3A4 inactivation by verapamil and diltiazem were determined using testosterone as the substrate. Testosterone 81-93 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-18 11038161-9 2000 Diltiazem, testosterone, and verapamil were metabolized predominantly by CYP3A4. Testosterone 11-23 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 11061575-3 2000 Concentration-effect of dexamethasone on CYP3A4-dependent testosterone 6-beta-hydroxylation was determined in human hepatocytes treated with 2 to 250 micromol/L dexamethasone. Testosterone 58-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 10901704-6 2000 Further evidence for involvement of CYP3A P450s was revealed by an anti-human CYP3A serum that inhibited the mono-N-dealkylation of both DP enantiomers and 6beta-hydroxylation of testosterone almost completely (i.e., >90%), whereas it only weakly inhibited (i.e., <15%) CYP1A1/2- or 2C19-mediated reactions. Testosterone 179-191 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 78-83 10877007-6 2000 Losartan and irbesartan inhibited CYP1A2- and CYP3A4-associated activities (ethoxyresorufin O-deethylation and testosterone 6beta-hydroxylation) with relatively weak affinities (IC50 values between 200 microM and 500 microM). Testosterone 111-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 10990198-5 2000 Cells were characterized for expression of CYP3A4 protein and CYP3A4 mediated metabolism towards midazolam and testosterone. Testosterone 111-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 43-49 10990198-5 2000 Cells were characterized for expression of CYP3A4 protein and CYP3A4 mediated metabolism towards midazolam and testosterone. Testosterone 111-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 62-68 10757990-2 2000 Enzyme kinetics for diazepam, erythromycin, nifedipine, and testosterone metabolism have been determined for both mutants and wild-type CYP3A4. Testosterone 60-72 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 136-142 10773015-6 2000 001) and CYP3A-selective testosterone 6beta-hydroxylation (r = 0.55, P <.02). Testosterone 25-37 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 9-14 10755318-14 2000 (4) DPPE inhibited the metabolism of testosterone by CYP3A4. Testosterone 37-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 10821163-5 2000 Ketoconazole exhibited potent inhibition of both CYP3A4-catalysed metabolism of phenanthrene, testosterone, diazepam (IC50 = 0.03-0.5 microM) and CYP1A1-catalysed deethylation of 7-ethoxycoumarin (0.33 microM). Testosterone 94-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 49-55 10640508-4 2000 Except for nifedipine, all calcium channel blockers showed increased inhibitory potency toward CYP3A activities (testosterone 6beta-hydroxylation and midazolam 1"-hydroxylation) after 30-min preincubation with NADPH. Testosterone 113-125 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-100 10755318-18 2000 DPPE inhibits testosterone metabolism by interacting at two sites on CYP3A4, the first correlating with its K(S) value to bind the substrate site and the second, with its EC50 value to enhance HA binding to the heme iron. Testosterone 14-26 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 69-75 10647906-4 1999 Methylenedioxyphenyl compounds which possess a bulky structure such as 1,4-benzothiazine showed substantial inhibition of S-warfarin 7-hydroxylation catalysed by CYP2C9, S-mephenytoin 4"-hydroxylation by CYP2C19, bufuralol 1"-hydroxylation by CYP2D6, and testosterone 6beta-hydroxylation by CYP3A4. Testosterone 255-267 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 291-297 10603245-1 1999 The standard method to evaluate CYP3A inhibition is to study the conversion of the specific CYP3A probe testosterone to its 6 beta-hydroxy metabolite in human liver microsomes, in the absence and presence of potential inhibitors. Testosterone 104-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 10603245-1 1999 The standard method to evaluate CYP3A inhibition is to study the conversion of the specific CYP3A probe testosterone to its 6 beta-hydroxy metabolite in human liver microsomes, in the absence and presence of potential inhibitors. Testosterone 104-116 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 92-97 10630892-4 1999 CYP3A4 enzyme formats incubated with anabolic steroids, testosterone, 17alpha-methyltestosterone, metandienone, boldenone and 4-chloro-1,2-dehydro-17alpha-methyltestosterone, produced 6beta-hydroxyl metabolites identified as trimethylsilyl (TMS)-ethers by a gas chromatography-mass spectrometry (GC-MS) method. Testosterone 56-68 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 10597902-2 1999 The most pronounced effects were observed with terfenadine, astemizole and loratadine which inhibited CYP3A4-mediated testosterone 6beta-hydroxylation (IC50 of 23, 21 and 32 microM, respectively) and CYP2D6-mediated dextromethorphan O-demethylation (IC50 of 18, 36 and 15 microM, respectively). Testosterone 118-130 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-108 10460798-2 1999 Growth conditions for Escherichia coli transformed with the bicistronic construct affected expression levels of CYP3A4 and NPR; an excess of NPR over P-450 in membrane preparations enhanced CYP3A4-dependent testosterone 6beta-hydroxylation activities of the CYP3A4/NPR membranes. Testosterone 207-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 190-196 10534309-4 1999 These values were highly correlated with the 6beta-hydroxylation activity of testosterone, a marker substrate of CYP3A4 (r = 0.977 and 0.900 for R(+)- and S(-)-gallopamil, respectively, p <.001). Testosterone 77-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 113-119 10525096-7 1999 Therefore, mAb(3A4a) was used to assess the quantitative role of CYP3A4/5 to the metabolism of testosterone and diazepam in five human liver microsomes. Testosterone 95-107 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 65-71 10548319-2 1999 A genetic variant of CYP3A4, a gene involved in the oxidative deactivation of testosterone, has been associated recently with prostate cancer development in Caucasians. Testosterone 78-90 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 21-27 10460798-2 1999 Growth conditions for Escherichia coli transformed with the bicistronic construct affected expression levels of CYP3A4 and NPR; an excess of NPR over P-450 in membrane preparations enhanced CYP3A4-dependent testosterone 6beta-hydroxylation activities of the CYP3A4/NPR membranes. Testosterone 207-219 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 190-196 10460798-5 1999 Apparent maximal activities of testosterone 6beta-hydroxylation in CYP3A4/NPR membranes were obtained when the molar ratio of CYP3A4/NPR/b(5) was adjusted to 1:2:1 by mixing membranes containing each protein. Testosterone 31-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 67-73 10460798-5 1999 Apparent maximal activities of testosterone 6beta-hydroxylation in CYP3A4/NPR membranes were obtained when the molar ratio of CYP3A4/NPR/b(5) was adjusted to 1:2:1 by mixing membranes containing each protein. Testosterone 31-43 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 126-132 10462503-5 1999 The testosterone 6beta-hydroxylation for CYP3A4 and chlorzoxazone 6-hydroxylation activity for CYP2E1 ranged from 30 to 505 pmol/mg/min (16-fold) and from 0.59 to 2.73 nmol/mg/ml (3.6-fold), respectively. Testosterone 4-16 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 41-47 10496649-8 1999 On the other hand, the transfected cells of early passages were much more metabolically active, and metabolized standard CYP3A4 substrates (e.g., testosterone and nifedipine) as much as 100 times faster than untransfected cells. Testosterone 146-158 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 121-127 9719084-2 1998 The goal of this study was to evaluate the effect of CYP3A4, a gene associated with the oxidative deactivation of testosterone, on the clinical presentation of prostate cancers. Testosterone 114-126 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 53-59 10334871-5 1999 Here we demonstrate that allowing human P450 reductase, CYP3A4, and cytochrome b5 to associate in an in vivo-like system, by coexpressing all three proteins together in Escherichia coli for the first time, the turnover of both nifedipine and testosterone by CYP3A4 is increased in the presence of cytochrome b5. Testosterone 242-254 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 56-62 10334871-5 1999 Here we demonstrate that allowing human P450 reductase, CYP3A4, and cytochrome b5 to associate in an in vivo-like system, by coexpressing all three proteins together in Escherichia coli for the first time, the turnover of both nifedipine and testosterone by CYP3A4 is increased in the presence of cytochrome b5. Testosterone 242-254 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 258-264 10215637-5 1999 We show that testosterone inhibited the CYP2D6-mediated bufuralol 1"-hydroxylase activity in bacterial membranes containing both CYP2D6 and CYP3A4 but not in membranes containing CYP2D6 alone. Testosterone 13-25 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 140-146 9918590-2 1999 The loss of testosterone 6beta-hydroxylation activity was time- and concentration-dependent as well as requiring metabolism of mifepristone in a purified CYP-3A4 reconstituted system. Testosterone 12-24 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-161 9732391-4 1998 932, P < .01) only with 6beta-hydroxylation of testosterone, a marker substrate for CYP3A4. Testosterone 50-62 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 87-93 20654528-4 1999 The results indicate that CYP3A4 shows an autocatalytic reaction kinetic probably due to two binding sites for testosterone. Testosterone 111-123 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-32 9820175-5 1998 Specific substrates of CYP included testosterone (catalysed by CYP3A4), paclitaxel (CYP2C8), 7-ethoxyresorufin (CYP1A1, CYP1A2), coumarin (CYP2A6), aniline (CYP2E1) and (+/-)-bufuralol (CYP2D6). Testosterone 36-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 63-69 9806945-0 1998 Comparative studies of in vitro inhibition of cytochrome P450 3A4-dependent testosterone 6beta-hydroxylation by roxithromycin and its metabolites, troleandomycin, and erythromycin. Testosterone 76-88 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-65 9806945-3 1998 Of roxithromycin and its studied metabolites, M3 was the most potent in inhibiting CYP3A4-dependent testosterone 6beta-hydroxylation by human liver microsomes and was activated to the inhibitory P450.Fe2+-metabolite complex to the greatest extent. Testosterone 100-112 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 83-89 9616193-5 1998 In a panel of 14 human liver microsomal preparations, the rate of dealkylation showed a highly significant correlation with CYP3A-mediated testosterone 6beta-hydroxylation but not with reactions of seven other CYP isoforms. Testosterone 139-151 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 124-129 14577225-0 1998 Thin-layer chromatographic analysis of human CYP3A-catalyzed testosterone 6 beta-hydroxylation. Testosterone 61-73 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-50 10660343-4 1998 CYP3A4 is involved in the metabolism of numerous biologically active compounds, including testosterone. Testosterone 90-102 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9531515-1 1998 The major pathway of testosterone oxidation by human liver microsomes is the formation of 6beta-hydroxytestosterone, which is catalyzed by CYP3A4/5 and which accounts for 75-80% of all metabolites formed. Testosterone 21-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 139-145 10022752-0 1998 Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Testosterone 167-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-24 10022752-0 1998 Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Testosterone 167-179 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 26-31 10022752-1 1998 The effect of ionic strength, assay constituents, alpha-naphthoflavone (aNF), terfenadine and testosterone on human CYP3A mediated midazolam (MDZ) 1"-hydroxylation (MDZ 1"-OH) and 4-hydroxylation (MDZ 4-OH) in vitro was examined. Testosterone 94-106 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 116-121 10022752-11 1998 Testosterone (10 and 100 microM) regioselectively stimulated (up to 269%) MDZ 4-OH formation by adult liver microsomes and expressed CYP3A4. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 133-139 9278209-3 1997 The probe substrates were phenacetin (CYP1A2), tolbutamide (CYP2C9), chlorzoxazone (CYP2E1) and testosterone (CYP3A4). Testosterone 96-108 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 110-116 9485522-8 1997 CYP3A4 (testosterone 6 beta-hydroxylation) activity was strongly inhibited by terfenadine with a Ki value of 25 microM, whereas epinastine had no effect at up to 100 microM. Testosterone 8-20 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-6 9402952-6 1997 The drugs known to be inducers of CYP3A4 in humans significantly increased a CYP isoform in pigs catalyzing 6 beta-hydroxylation of testosterone and 2-hydroxylation of EE2, whereas drugs not reported to have clinical interactions with EE2 had no or only marginal effect. Testosterone 132-144 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 34-40 9486958-0 1997 HIV protease inhibitors, saquinavir, indinavir and ritonavir: inhibition of CYP3A4-mediated metabolism of testosterone and benzoxazinorifamycin, KRM-1648, in human liver microsomes. Testosterone 106-118 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 76-82 9266706-7 1997 Conversely, the conversion of testosterone into its 6beta derivative is essentially supported by CYP3A4. Testosterone 30-42 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 97-103 9298257-9 1997 Induction of CYP3A4, measured as testosterone 6 beta-hydroxylation, was found to be dose-dependent, treatment duration-dependent, and reversible. Testosterone 33-45 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 13-19 9193880-6 1997 In human liver microsomes, only one protein band which comigrated with human CYP3A4 was recognized by this antibody and the relative blotting intensity of this protein band correlated significantly with human CYP3A4-catalyzed testosterone 6 beta-hydroxylase activities (r = 0.96). Testosterone 226-238 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-83 9186495-8 1997 Interestingly, we found that testosterone 6 beta-hydroxylation by CYP3A4 was stimulated by CYP1A2 (and also by a modified form in which the first 36 residues of the native human protein were removed) and CYP1A1 as well as by b5, and such stimulations were not seen when other P450 proteins (e.g., CYP2C10, 2D6, or 2E1) were added to the reconstituted systems. Testosterone 29-41 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 66-72 9193880-6 1997 In human liver microsomes, only one protein band which comigrated with human CYP3A4 was recognized by this antibody and the relative blotting intensity of this protein band correlated significantly with human CYP3A4-catalyzed testosterone 6 beta-hydroxylase activities (r = 0.96). Testosterone 226-238 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 209-215 9152594-9 1997 In addition, PCP inhibited CYP3A-mediated testosterone 6 beta-hydroxylation by 50%. Testosterone 42-54 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 27-32 9157990-5 1997 Rifampin (1 microM, 96-h exposure) was a particularly potent inducer of ifosfamide and cyclophosphamide 4-hydroxylation, as well as of CYP3A protein levels and CYP3A-dependent testosterone 6beta-hydroxylation. Testosterone 176-188 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 160-165 9152594-10 1997 Furthermore, the relative intensity of CYP3A immunoreactive proteins significantly correlated with testosterone 6 beta-hydroxylation and with PCP metabolite formation (except for the unknown metabolite). Testosterone 99-111 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 39-44 21781753-6 1997 The expressed enzyme was shown to catalyze the 6beta-hydroxylation of testosterone, which could also be observed in a V79 cell line expressing human CYP3A4. Testosterone 70-82 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 149-155 9107550-2 1997 Cytochrome P450 3A4 is known to catalyze the metabolism of both endogenous substrates (such as the 6 beta-hydroxylation of testosterone) and many important therapeutic agents, including the N-demethylation of erythromycin. Testosterone 123-135 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 0-19 9107550-11 1997 We conclude from these studies that testosterone and erythromycin mutually inhibit the metabolism of each other, consistent with the fact that CYP 3A4 catalyzes the metabolism of both substrates. Testosterone 36-48 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 143-150 9249858-10 1997 The CYP3A4 activity (testosterone) detected in minipigs was higher than the activity in conventional pigs. Testosterone 21-33 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 4-10 9023313-12 1997 Testosterone 6beta-hydroxylation (mediated by CYP3A4), 7-ethylresorufin O-deethylation (CYP1A2) and tolbutamide methyl hydroxylation (CYP2C9/10), but not aniline 4-hydroxylation (CYP2E1), were inhibited effectively by parathion. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 8968357-7 1996 The 3-hydroxylation of quinine showed an excellent correlation (r = 0.986, P < .001) with 6 beta-hydroxylation of testosterone, a marker substrate for CYP3A4. Testosterone 117-129 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 154-160 8956327-8 1996 The appropriate transfected monolayers metabolized the CYP2A6 substrate coumarin and the CYP3A4 substrates testosterone and nifedipine. Testosterone 107-119 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 89-95 8959645-0 1996 Effects of erythromycin and roxithromycin on oxidation of testosterone and nifedipine catalyzed by CYP3A4 in human liver microsomes. Testosterone 58-70 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 99-105 8806738-3 1996 Activity was tested by 6 beta-hydroxylation of testosterone for cytochrome P450 3A4 and by cytochrome c reduction for NADPH-cytochrome P450 reductase. Testosterone 47-59 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 64-83 8866826-8 1996 Human CYP3A4 and rat CYP3A2 had high testosterone 2 beta- and 6 beta-hydroxylation activities in a modified reconstituted system with a lipid mixture. Testosterone 37-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-12 8817061-7 1996 However, no CBZ-E (or any metabolite) was recovered from any whole-cell incubation even though hCYP3A4 cells readily converted testosterone to 6 beta-hydroxytestosterone. Testosterone 127-139 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 95-102 8781778-11 1996 Comparative studies with human liver microsomes suggested the possible involvement of CYP3A enzymes in the intestinal catalysis of testosterone 6 beta-hydroxylation similar to those observed with human hepatic CYP3A. Testosterone 131-143 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 8619853-3 1996 Using purified cDNA-expressed CYP3A4 incorporated into membranous vesicles made from microsomal phospholipids, rates of nifedipine and testosterone oxidation of about 60 nmol/nmol P450/min were achieved, whereas similar reconstitution into dilauroyl-phosphatidylcholine micelles was unsuccessful. Testosterone 135-147 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 30-36 7575636-4 1995 The 6 beta-hydroxylation activity of testosterone, which is increased in CYP3A4-expressing cells compared to vector-transfected cells, showed reduced activity after incubation with 1 microM tiamulin and was completely reduced to background level after incubation with 2, 5 and 10 microM tiamulin. Testosterone 37-49 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 73-79 8548776-4 1996 Docetaxel hydroxylation correlated only with the CYP3A content of microsomes and with CYP3A-dependent 6 beta-hydroxylation of testosterone and 16-hydroxylation of dehydroepiandrosterone. Testosterone 126-138 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 8548776-5 1996 The formation of hydroxydocetaxel was strongly reduced by CYP3A inhibitors such as ketoconazole, midazolam, erythromycin, testosterone, orphenadrine, and troleandomycin, whereas quinidine (CYP2D6), hexobarbital, tolbutamide, and mephenytoin (CYP2C) had no or little effect. Testosterone 122-134 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 58-63 8561495-0 1996 Roles of cytochrome b5 in the oxidation of testosterone and nifedipine by recombinant cytochrome P450 3A4 and by human liver microsomes. Testosterone 43-55 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-105 7833826-7 1994 Testosterone 6 beta-hydroxylation mediated by CYP3A4 was stimulated by ANF and metabolites with substitutions at positions 5,6 or 7,8. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 46-52 7587944-3 1995 Although testosterone 6 beta-hydroxylation [CYP3A(4)] has been shown to be the principal enzyme involved in the first step in terfenadine"s biotransformation (formation of azacyclonol and terfenadine alcohol), the enzymes catalyzing the subsequent metabolic steps in the conversion of terfenadine alcohol to azacyclonol and terfenadine acid have not been identified. Testosterone 9-21 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 44-52 7628296-9 1995 Therefore, compounds interacting with CYP3A proteins are expected to cause drug-drug interactions (i.e. the antimycotics ketoconazole and clotrimazole, the steroids ethinylestradiol and testosterone, the ergots, the calcium channel blocker nifedipine, and the immunosuppressants FK-506 and rapamycin). Testosterone 186-198 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 38-43 7720517-5 1995 We found a strong correlation between formation of the two main metabolites and testosterone 6 beta-hydroxylation (correlation 0.98 and 0.95), a marker for CYP3A. Testosterone 80-92 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 156-161 7720520-7 1995 Of the CYP3A4 inhibitor probes used, troleandomycin proved to be the most specific for testosterone 6 beta-hydroxylation. Testosterone 87-99 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 7-13 8265621-1 1993 Human cytochrome P450 3A4 is recognized as the catalyst for the oxygen-dependent metabolism of a diverse group of medically important chemicals, including the immunosuppressive agent cyclosporin; macrolide antibiotics, such as erythromycin; drugs such as benzphetamine, nifedipine, and cocaine; and steroids; such as cortisol and testosterone to name but a few. Testosterone 330-342 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 6-25 7903909-7 1994 The formation of metabolite M4 was substantially reduced both by antibody directed against CYP3A and by the addition of CYP3A substrates such as orphenadrine, erythromycin, troleandomycin, and testosterone. Testosterone 193-205 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 120-125 8424894-0 1993 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. Testosterone 77-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 12-30 8424894-0 1993 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. Testosterone 77-89 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 32-37 8424894-5 1993 Testosterone hydroxylations at 6 beta-, 2 beta-, 15 alpha- and 15 beta-positions were associated with CYP3A isoform(s) in adult liver, because they were strongly inhibited by midazolam, a known substrate for CYP3A4 and by anti-CYP3A4 antibody. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 102-107 8424894-5 1993 Testosterone hydroxylations at 6 beta-, 2 beta-, 15 alpha- and 15 beta-positions were associated with CYP3A isoform(s) in adult liver, because they were strongly inhibited by midazolam, a known substrate for CYP3A4 and by anti-CYP3A4 antibody. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 208-214 8424894-5 1993 Testosterone hydroxylations at 6 beta-, 2 beta-, 15 alpha- and 15 beta-positions were associated with CYP3A isoform(s) in adult liver, because they were strongly inhibited by midazolam, a known substrate for CYP3A4 and by anti-CYP3A4 antibody. Testosterone 0-12 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 227-233 34196520-4 2021 We have used hydrogen-deuterium exchange mass spectrometry to investigate the impact of binding of CPR and of three different substrates (7-benzyloxy-4-trifluoromethyl-coumarin, testosterone, and progesterone) on the conformational dynamics of CYP3A4. Testosterone 178-190 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 244-250 34326139-6 2021 Co-incubation with testosterone (alternative CYP3A substrate) or ketoconazole (direct CYP3A inhibitor) attenuated the rate of inactivation whereas the inclusion of glutathione and catalase did not confer such protection. Testosterone 19-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 45-50 34326139-6 2021 Co-incubation with testosterone (alternative CYP3A substrate) or ketoconazole (direct CYP3A inhibitor) attenuated the rate of inactivation whereas the inclusion of glutathione and catalase did not confer such protection. Testosterone 19-31 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 86-91 34473615-4 2021 METHODS: 6beta-Hydroxylated testosterone formation was selected to probe the CYP3A activity in human liver microsomes. Testosterone 28-40 cytochrome P450 family 3 subfamily A member 4 Homo sapiens 77-82