PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32565960-5 2020 Gain- and loss-of-function studies were conducted by transfecting colon cancer cells with FXR siRNA and treating them with the FXR agonist GW4064. GW 4064 139-145 nuclear receptor subfamily 1 group H member 4 Homo sapiens 127-130 32846898-5 2020 FXR agonists chenodeoxycholic acid (CDCA) and GW4064 stimulated OCT2-mediated 3H-MPP+ uptake in human renal proximal tubular cells (RPTEC/TERT1 cells) and OCT2-CHO-K1 cells. GW 4064 46-52 nuclear receptor subfamily 1 group H member 4 Homo sapiens 0-3 32341465-8 2020 Farnesoid X receptor (FXR) inhibitor glycine-beta-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). GW 4064 143-149 nuclear receptor subfamily 1 group H member 4 Homo sapiens 22-25 32341465-8 2020 Farnesoid X receptor (FXR) inhibitor glycine-beta-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). GW 4064 143-149 nuclear receptor subfamily 1 group H member 4 Homo sapiens 69-72 32341465-8 2020 Farnesoid X receptor (FXR) inhibitor glycine-beta-muricholic acid or FXR knockdown reversed the downregulation of PepT1 expression by CDCA and GW4064 (another FXR agonist). GW 4064 143-149 nuclear receptor subfamily 1 group H member 4 Homo sapiens 69-72 32565960-9 2020 The FXR agonist GW4064 significantly inhibited the proliferation of cells but promoted the transcriptional activity of beta-catenin. GW 4064 16-22 nuclear receptor subfamily 1 group H member 4 Homo sapiens 4-7 31911244-6 2020 Mechanistically, GW4064, an FXR agonist, was carried out to verify the mechanisms of geniposide in human HepG2 and Caco2 cells. GW 4064 17-23 nuclear receptor subfamily 1 group H member 4 Homo sapiens 28-31 30428773-4 2019 Here, we aimed to investigate whether FXR activation by its synthetic agonist GW4064 has a therapeutic effect on endometriosis and the underlying molecular mechanisms. GW 4064 78-84 nuclear receptor subfamily 1 group H member 4 Homo sapiens 38-41 31779647-12 2019 CONCLUSIONS: Upregulated FXR by GW4064 can obviously suppress OS cell development, and the suppressive effects may rely on miR-23b-3p/CCNG1 pathway. GW 4064 32-38 nuclear receptor subfamily 1 group H member 4 Homo sapiens 25-28 31779647-4 2019 Their correlations were analyzed by Pearson"s test and verified by the introduction of FXR agonist, GW4064. GW 4064 100-106 nuclear receptor subfamily 1 group H member 4 Homo sapiens 87-90 31561852-3 2019 We evaluated pharmacological activation of FXR with the synthetic agonist GW4064 using comprehensive proteomic analysis in colorectal cancer cell lines (HCT116, SW480, and DLD1). GW 4064 74-80 nuclear receptor subfamily 1 group H member 4 Homo sapiens 43-46 31095863-8 2019 Knockdown of CYP7A1 via small interfering RNA or activation of FXR by GW4064 blocks the effect of TMAO-induced lipogenesis in palmitic acid-treated HepG2 cells. GW 4064 70-76 nuclear receptor subfamily 1 group H member 4 Homo sapiens 63-66 30428773-10 2019 Coimmunoprecipitation assay and chromatin immunoprecipitation analysis revealed that FXR was able to compete with cyclic AMP response element-binding (CREB) protein for binding to a common sequence on the aromatase promoter region after GW4064 treatment in ESCs. GW 4064 237-243 nuclear receptor subfamily 1 group H member 4 Homo sapiens 85-88 30747230-5 2019 Conversely, the FXR agonist GW4064 synergistically enhanced bile acid-induced CDX2 promoter activity. GW 4064 28-34 nuclear receptor subfamily 1 group H member 4 Homo sapiens 16-19 30902657-0 2019 Farnesoid X receptor agonist GW4064 indirectly inhibits HCV entry into cells via down-regulating scavenger receptor class B type I. Farnesoid X receptor (FXR) agonists play important regulatory roles in bile acid, lipid and glucose metabolism in vitro and in vivo. GW 4064 29-35 nuclear receptor subfamily 1 group H member 4 Homo sapiens 154-157 30902657-2 2019 This study investigated the effect and mechanism of FXR agonist GW4064 against HCV in vitro to explore the potential application of FXR agonists. GW 4064 64-70 nuclear receptor subfamily 1 group H member 4 Homo sapiens 52-55 30902657-4 2019 GW4064 down-regulated the expression of scavenger receptor class B type I protein via FXR and thereby indirectly inhibited HCV entry into cells, leading to interruption of HCV life cycle. GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 86-89 30176263-3 2018 We showed that FXR is expressed in human CAFs isolated from four patients and treatment with the selective FXR agonist GW4064 decreased CAF migration, stress-fiber formation and contractility. GW 4064 119-125 nuclear receptor subfamily 1 group H member 4 Homo sapiens 15-18 30176263-3 2018 We showed that FXR is expressed in human CAFs isolated from four patients and treatment with the selective FXR agonist GW4064 decreased CAF migration, stress-fiber formation and contractility. GW 4064 119-125 nuclear receptor subfamily 1 group H member 4 Homo sapiens 107-110 29958417-4 2018 FXR agonists (chenodeoxycholic acid, GW4064, and obeticholic acid):but not an antagonist (guggulsterone)—induced actin polymerization and expression of N-cadherin and phosphorylated focal adhesion kinase, although they were less effective than transforming growth factor beta (TGF-beta). GW 4064 37-43 nuclear receptor subfamily 1 group H member 4 Homo sapiens 0-3 30106441-13 2018 In the present study, activation of FXR by GW4064 increased CCNG2 expression via suppression of miR-135A1 expression, and the FXR/miR-135A1/CCNG2 axis was demonstrated to be involved in mediating cell proliferation. GW 4064 43-49 nuclear receptor subfamily 1 group H member 4 Homo sapiens 36-39 30106441-14 2018 In conclusion, activation of FXR by GW4064 suppresses cell proliferation and causes cell cycle arrest in CRC, and the miR-135A1/CCNG2 pathway was suggested to be involved in this step. GW 4064 36-42 nuclear receptor subfamily 1 group H member 4 Homo sapiens 29-32 28787755-1 2017 GW4064 is a small molecule known to be an agonist of the nuclear farnesoid X receptor (FXR). GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 87-90 29849798-3 2018 Human gastric cell lines were treated with chenodeoxycholic acid (CDCA) or FXR agonist GW4064. GW 4064 87-93 nuclear receptor subfamily 1 group H member 4 Homo sapiens 75-78 29351391-8 2018 DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 microM), inhibited wound closure. GW 4064 97-103 nuclear receptor subfamily 1 group H member 4 Homo sapiens 84-87 28267333-3 2017 GW4064 and chenodeoxycholic acid (two specific FXR agonists) treatment of HepG2 cells led to a significant increase in the mRNA level of UGT2B10. GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 47-50 28787755-2 2017 We found that GW4064 inhibits the NLR family CARD domain containing 3 (NLRP3) inflammasome activation in an FXR-independent manner as evidenced by its similar inhibitory effect on NLRP3 inflammasome activation in FXR-deficient macrophages. GW 4064 14-20 nuclear receptor subfamily 1 group H member 4 Homo sapiens 108-111 28787755-2 2017 We found that GW4064 inhibits the NLR family CARD domain containing 3 (NLRP3) inflammasome activation in an FXR-independent manner as evidenced by its similar inhibitory effect on NLRP3 inflammasome activation in FXR-deficient macrophages. GW 4064 14-20 nuclear receptor subfamily 1 group H member 4 Homo sapiens 213-216 28787755-5 2017 These results not only necessitate cautious interpretation of the biological function of GW4064 as an FXR agonist, but also provide a potential therapeutic approach using GW4064 in the treatment of NLRP3-related diseases. GW 4064 89-95 nuclear receptor subfamily 1 group H member 4 Homo sapiens 102-105 27127878-3 2016 In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC. GW 4064 101-107 nuclear receptor subfamily 1 group H member 4 Homo sapiens 87-90 29283075-4 2017 RESULTS: In human hepatocytes, treatment with the FXR agonists GW4064 (1.0 microM) and WAY362450 (0.1 microM) did not significantly induce the mRNA expression of BACS and BAT genes. GW 4064 63-69 nuclear receptor subfamily 1 group H member 4 Homo sapiens 50-53 27471003-4 2016 Activation of FXR by chenodeoxycholic acid (CDCA) or GW4064 significantly decreased PLA2G12B expression in HepG2 cells. GW 4064 53-59 nuclear receptor subfamily 1 group H member 4 Homo sapiens 14-17 28066584-9 2016 FXR agonist GW4064 remarkably enhanced and FXR antagonist Z-Guggulsterone significantly inhibited EMT changes in TGF-beta1-treated HBE cells. GW 4064 12-18 nuclear receptor subfamily 1 group H member 4 Homo sapiens 0-3 26646674-4 2017 METHODS: This study investigated the effect of LQ, metformin [an activator of activated AMP-activated protein kinase (AMPK)] and GW4064 [a ligand of farnesoid X receptor (FXR)] on mitochondrial dysfunction and oxidative stress induced by serum deprivation as well as its molecular mechanism, as assessed by immunoblot and flow cytometer assays. GW 4064 129-135 nuclear receptor subfamily 1 group H member 4 Homo sapiens 149-169 26646674-4 2017 METHODS: This study investigated the effect of LQ, metformin [an activator of activated AMP-activated protein kinase (AMPK)] and GW4064 [a ligand of farnesoid X receptor (FXR)] on mitochondrial dysfunction and oxidative stress induced by serum deprivation as well as its molecular mechanism, as assessed by immunoblot and flow cytometer assays. GW 4064 129-135 nuclear receptor subfamily 1 group H member 4 Homo sapiens 171-174 26646674-9 2017 LQ also induced protein and mRNA expression of both FXR as well as small heterodimer partner, which is important since treatment with FXR ligand GW4064 protected hepatocytes against cell death and mitochondrial damage induced by serum deprivation. GW 4064 145-151 nuclear receptor subfamily 1 group H member 4 Homo sapiens 52-55 26646674-9 2017 LQ also induced protein and mRNA expression of both FXR as well as small heterodimer partner, which is important since treatment with FXR ligand GW4064 protected hepatocytes against cell death and mitochondrial damage induced by serum deprivation. GW 4064 145-151 nuclear receptor subfamily 1 group H member 4 Homo sapiens 134-137 27758768-3 2016 In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6alpha-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically. GW 4064 79-85 nuclear receptor subfamily 1 group H member 4 Homo sapiens 28-31 27758768-3 2016 In this study, we show that FXR is present in human platelets and FXR ligands, GW4064 and 6alpha-ethyl-chenodeoxycholic acid, modulate platelet activation nongenomically. GW 4064 79-85 nuclear receptor subfamily 1 group H member 4 Homo sapiens 66-69 27758768-9 2016 The atheroprotective effects of GW4064, with its novel antiplatelet effects, indicate FXR as a potential target for the prevention of atherothrombotic disease. GW 4064 32-38 nuclear receptor subfamily 1 group H member 4 Homo sapiens 86-89 27251172-4 2016 In HepaRG cells, FXR agonists (6-ethyl chenodeoxycholic acid and GW4064), but no antagonist, and an FXR-unrelated bile salt inhibited viral mRNA, DNA, and protein production (IC50, 0.1-0.5 muM) and reduced covalently closed circular DNA pool size. GW 4064 65-71 nuclear receptor subfamily 1 group H member 4 Homo sapiens 17-20 26545738-4 2016 We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA-MB-231 and MDA-MB-468 (triple negative). GW 4064 107-113 nuclear receptor subfamily 1 group H member 4 Homo sapiens 48-51 26899873-4 2016 Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW 4064 76-82 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-67 26450152-4 2016 In this study, we reported that FXR agonist GW4064 reduced high glucose induced human mesangial cells (HMCs) inflammation, fibrosis and proliferation by downregulating visfatin expression, which can be blunted by exogenous visfatin treatment. GW 4064 44-50 nuclear receptor subfamily 1 group H member 4 Homo sapiens 32-35 26324224-4 2015 The treatment of FXR agonist GW4064/antagonist guggulsterone (Gug.) GW 4064 29-35 nuclear receptor subfamily 1 group H member 4 Homo sapiens 17-20 26583035-6 2015 Human kidney 2 (HK2) cells were exposed to high glucose with or without the FXR agonist GW4064 or when FXR mRNA was silenced. GW 4064 88-94 nuclear receptor subfamily 1 group H member 4 Homo sapiens 76-79 26583035-8 2015 HK2 cells exposed to high glucose had reduced FXR expression and increased MCP-1, TGF-beta1, fibronectin and collagen IV expression, which was reversed in the presence of GW4064. GW 4064 171-177 nuclear receptor subfamily 1 group H member 4 Homo sapiens 46-49 25934227-3 2015 Evaluation of the co-crystal structures of the widely used FXR agonist GW4064 and related compounds in complex with the FXR ligand binding domain indicated that their disubstituted isoxazole moiety is especially relevant for FXR activation. GW 4064 71-77 nuclear receptor subfamily 1 group H member 4 Homo sapiens 59-62 25934227-3 2015 Evaluation of the co-crystal structures of the widely used FXR agonist GW4064 and related compounds in complex with the FXR ligand binding domain indicated that their disubstituted isoxazole moiety is especially relevant for FXR activation. GW 4064 71-77 nuclear receptor subfamily 1 group H member 4 Homo sapiens 120-123 25934227-3 2015 Evaluation of the co-crystal structures of the widely used FXR agonist GW4064 and related compounds in complex with the FXR ligand binding domain indicated that their disubstituted isoxazole moiety is especially relevant for FXR activation. GW 4064 71-77 nuclear receptor subfamily 1 group H member 4 Homo sapiens 120-123 26098428-5 2015 Distinctly from CDCA, MG132 prevented SHP and an exogenous FXR agonist, GW4064 from reducing HIF-1alpha protein. GW 4064 72-78 nuclear receptor subfamily 1 group H member 4 Homo sapiens 59-62 25010412-8 2014 In addition, cell-permeable bile acids reduced HDL endocytosis by farnesoid X receptor (FXR) activation: chenodeoxycholate and the non-steroidal FXR agonist GW4064 reduced HDL endocytosis, whereas selective CE uptake was unaltered. GW 4064 157-163 nuclear receptor subfamily 1 group H member 4 Homo sapiens 88-91 25496033-8 2015 FXR knockdown abolished the inhibition of 3-[2-[2-chloro-4-[[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]-Benzoic acid (GW4064) on JNK phosphorylation and ROS production induced by H2O2in HepG2 cells. GW 4064 153-159 nuclear receptor subfamily 1 group H member 4 Homo sapiens 0-3 25499883-2 2015 Previous work has described GW4064 as an FXR agonist with an interesting activity profile. GW 4064 28-34 nuclear receptor subfamily 1 group H member 4 Homo sapiens 41-44 25466848-6 2015 RESULTS: 13 nuclear hormone receptor ligands were assayed, being GW4064 (FXR ligand) the most potent activator. GW 4064 65-71 nuclear receptor subfamily 1 group H member 4 Homo sapiens 73-76 25010412-8 2014 In addition, cell-permeable bile acids reduced HDL endocytosis by farnesoid X receptor (FXR) activation: chenodeoxycholate and the non-steroidal FXR agonist GW4064 reduced HDL endocytosis, whereas selective CE uptake was unaltered. GW 4064 157-163 nuclear receptor subfamily 1 group H member 4 Homo sapiens 145-148 24597548-0 2014 Synthetic FXR agonist GW4064 is a modulator of multiple G protein-coupled receptors. GW 4064 22-28 nuclear receptor subfamily 1 group H member 4 Homo sapiens 10-13 23916961-7 2014 RESULTS: GW4064 (5 mumol/L; 24 h), a specific FXR agonist, induced nuclear translocation of the receptor in T84 cells and attenuated Cl(-) secretory responses to both Ca(2+) and cAMP-dependent agonists. GW 4064 9-15 nuclear receptor subfamily 1 group H member 4 Homo sapiens 46-49 24597548-10 2014 Taken together, our results demonstrate identification of histamine receptors as alternate targets for GW4064, which not only necessitates cautious interpretation of the biological functions attributed to FXR using GW4064 as a pharmacological tool but also provides a basis for the rational designing of new pharmacophores for histamine receptor modulation. GW 4064 103-109 nuclear receptor subfamily 1 group H member 4 Homo sapiens 205-208 24597548-1 2014 The synthetic nuclear bile acid receptor (farnesoid X receptor [FXR]) agonist GW4064 is extensively used as a specific pharmacological tool to illustrate FXR functions. GW 4064 78-84 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-67 24597548-1 2014 The synthetic nuclear bile acid receptor (farnesoid X receptor [FXR]) agonist GW4064 is extensively used as a specific pharmacological tool to illustrate FXR functions. GW 4064 78-84 nuclear receptor subfamily 1 group H member 4 Homo sapiens 154-157 24597548-2 2014 We noticed that GW4064 activated empty luciferase reporters in FXR-deficient HEK-293T cells. GW 4064 16-22 nuclear receptor subfamily 1 group H member 4 Homo sapiens 63-66 24597548-9 2014 We also found that MCF-7 breast cancer cells, reported to undergo GW4064-induced apoptosis in an FXR-dependent manner, did not express FXR, and the GW4064-mediated apoptosis, also apparent in HEK-293T cells, could be blocked by selective histamine receptor regulators. GW 4064 66-72 nuclear receptor subfamily 1 group H member 4 Homo sapiens 97-100 23767959-2 2013 We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKtheta in the HepG2 cell line and in primary human hepatocytes. GW 4064 93-99 nuclear receptor subfamily 1 group H member 4 Homo sapiens 59-62 24321096-4 2014 In reporter assays, active SREBP-2 overexpression suppressed GW4064/FXR-mediated increase in reporter activities in regions containing the IR-1 motif (+848 to +5200) in the FGF19 gene. GW 4064 61-67 nuclear receptor subfamily 1 group H member 4 Homo sapiens 68-71 25388536-3 2014 The quest for synthetic non-steroidal FXR agonists with general drug likeliness and improved pharmacokinetic and - dynamic properties has started more than a decade ago: The first non-steroidal and selective FXR agonist with decent submicromolar potency, GW4064, was patented in 1998 and published in 2000. GW 4064 255-261 nuclear receptor subfamily 1 group H member 4 Homo sapiens 38-41 25388536-3 2014 The quest for synthetic non-steroidal FXR agonists with general drug likeliness and improved pharmacokinetic and - dynamic properties has started more than a decade ago: The first non-steroidal and selective FXR agonist with decent submicromolar potency, GW4064, was patented in 1998 and published in 2000. GW 4064 255-261 nuclear receptor subfamily 1 group H member 4 Homo sapiens 208-211 25388536-4 2014 Since then, many pharmaceutical companies have taken GW4064 as a structural template for their efforts in identifying novel patentable FXR agonists with the GW-derived trisubstituted isoxazole general structure. GW 4064 53-59 nuclear receptor subfamily 1 group H member 4 Homo sapiens 135-138 23928191-6 2013 When FXR was expressed in liver and intestinal cells the magnitude of the response to GW4064 and bile acids differs among FXR isoforms. GW 4064 86-92 nuclear receptor subfamily 1 group H member 4 Homo sapiens 5-8 23928191-6 2013 When FXR was expressed in liver and intestinal cells the magnitude of the response to GW4064 and bile acids differs among FXR isoforms. GW 4064 86-92 nuclear receptor subfamily 1 group H member 4 Homo sapiens 122-125 24463129-7 2014 CONCLUSION: GW4064 can up-regulate the expressions of FXR, PPARgamma2, adiponectin, AdipoR2 in 3T3-L1 preadipocytes and AdipoR2 in HepG2 cells. GW 4064 12-18 nuclear receptor subfamily 1 group H member 4 Homo sapiens 54-57 23680185-6 2013 In human hepatocytes, the activation of FXR with the agonist GW4064 resulted in a significant protection against cisplatin-induced toxicity. GW 4064 61-67 nuclear receptor subfamily 1 group H member 4 Homo sapiens 40-43 23680185-7 2013 In human hepatoma Alexander cells, with negligible endogenous expression of FXR, GW4064 also protected against cisplatin-induced toxicity, but only if they were previously transfected with FXR/RXR. GW 4064 81-87 nuclear receptor subfamily 1 group H member 4 Homo sapiens 189-192 23680185-9 2013 In both models, cisplatin, even in the absence of FXR agonists, such as bile acids and GW4064, was able to up-regulate FXR targets genes, which was due to FXR-mediated trans-activation of response elements in the promoter region. GW 4064 87-93 nuclear receptor subfamily 1 group H member 4 Homo sapiens 119-122 23680185-9 2013 In both models, cisplatin, even in the absence of FXR agonists, such as bile acids and GW4064, was able to up-regulate FXR targets genes, which was due to FXR-mediated trans-activation of response elements in the promoter region. GW 4064 87-93 nuclear receptor subfamily 1 group H member 4 Homo sapiens 119-122 23767959-2 2013 We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKtheta in the HepG2 cell line and in primary human hepatocytes. GW 4064 93-99 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-84 23688559-4 2013 Here we describe the use of the X-ray crystal structure of FXR complexed with the potent small molecule agonist GW4064 to design and synthesize a novel fluorescent, high-affinity probe (DY246) for time resolved fluorescence resonance energy transfer (TR-FRET) assays. GW 4064 112-118 nuclear receptor subfamily 1 group H member 4 Homo sapiens 59-62 23772048-3 2013 In human hepatocytes, both the endogenous FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 increased ADH1 mRNA, protein, and activity. GW 4064 110-116 nuclear receptor subfamily 1 group H member 4 Homo sapiens 89-92 23313557-6 2013 In HepG2 cells, GCs induced a decreased expression of FXR and SHP, and inhibited the regulatory effect of GW4064 on FXR-target genes. GW 4064 106-112 nuclear receptor subfamily 1 group H member 4 Homo sapiens 116-119 23541942-1 2013 Here we report that bile acid chenodeoxycholic acid (CDCA) and synthetic farnesoid X receptor (FXR) agonist GW4064 robustly induced tumor suppressor N-Myc downstream regulated gene 2 (NDRG2) expression in human hepatoma cells and primary hepatocytes. GW 4064 108-114 nuclear receptor subfamily 1 group H member 4 Homo sapiens 95-98 23313557-7 2013 In Alexander cells, only when they were transfected with FXR+RXR, GW4064 caused up-regulation of SHP and OSTbeta, and a down-regulation of CYP27A1. GW 4064 66-72 nuclear receptor subfamily 1 group H member 4 Homo sapiens 57-60 23313557-10 2013 Moreover, GCs have a synergistic effect on GW4064-induced FXR activation, whereas chenodeoxycholate and GW4064 have an additive effect. GW 4064 43-49 nuclear receptor subfamily 1 group H member 4 Homo sapiens 58-61 23101941-2 2012 GW4064 is a potent and selective FXR agonist and has become a tool compound to probe the physiological functions of FXR. GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 33-36 23878601-4 2013 Interestingly, activation of the farnesoid X receptor (FXR) through the bile acid ursodeoxycholic acid (UDCA) or synthetic FXR agonists, such as GW4064, can increase DDAH1 expression. GW 4064 145-151 nuclear receptor subfamily 1 group H member 4 Homo sapiens 55-58 23878601-4 2013 Interestingly, activation of the farnesoid X receptor (FXR) through the bile acid ursodeoxycholic acid (UDCA) or synthetic FXR agonists, such as GW4064, can increase DDAH1 expression. GW 4064 145-151 nuclear receptor subfamily 1 group H member 4 Homo sapiens 123-126 23101941-2 2012 GW4064 is a potent and selective FXR agonist and has become a tool compound to probe the physiological functions of FXR. GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 116-119 23101941-3 2012 Until now, the mechanism of GW4064 entering and leaving the FXR pocket is still poorly understood. GW 4064 28-34 nuclear receptor subfamily 1 group H member 4 Homo sapiens 60-63 23101941-4 2012 Here, we report a computational study of GW4064 unbinding pathways from FXR by using several molecular dynamics (MD) simulation techniques. GW 4064 41-47 nuclear receptor subfamily 1 group H member 4 Homo sapiens 72-75 23101941-5 2012 Based on the crystal structure of FXR in complex with GW4064, conventional MD was first used to refine the binding and check the stability of GW4064 in the FXR pocket. GW 4064 54-60 nuclear receptor subfamily 1 group H member 4 Homo sapiens 34-37 23101941-5 2012 Based on the crystal structure of FXR in complex with GW4064, conventional MD was first used to refine the binding and check the stability of GW4064 in the FXR pocket. GW 4064 54-60 nuclear receptor subfamily 1 group H member 4 Homo sapiens 156-159 23101941-5 2012 Based on the crystal structure of FXR in complex with GW4064, conventional MD was first used to refine the binding and check the stability of GW4064 in the FXR pocket. GW 4064 142-148 nuclear receptor subfamily 1 group H member 4 Homo sapiens 34-37 23101941-5 2012 Based on the crystal structure of FXR in complex with GW4064, conventional MD was first used to refine the binding and check the stability of GW4064 in the FXR pocket. GW 4064 142-148 nuclear receptor subfamily 1 group H member 4 Homo sapiens 156-159 23101941-6 2012 Random acceleration MD simulations were then performed to explore the possible unbinding pathways of GW4064 from FXR. GW 4064 101-107 nuclear receptor subfamily 1 group H member 4 Homo sapiens 113-116 22817871-4 2012 In the present study, we for the first time identified that in human hepatoma cell line HepG2 the activation of FXR by the natural agonist chenodeoxycholic acid (CDCA) and the synthetic specific agonist GW4064 upregulated CISH at both transcriptional and translational levels, and inhibited interleukin (IL)6-induced STAT5 activation. GW 4064 203-209 nuclear receptor subfamily 1 group H member 4 Homo sapiens 112-115 22579649-3 2012 In the present study, we examined the effects of acyclic retinoid (ACR), a synthetic retinoid targeting RXRalpha, plus GW4064, a ligand for FXR, on the growth of human HCC cells. GW 4064 119-125 nuclear receptor subfamily 1 group H member 4 Homo sapiens 140-143 22579649-9 2012 Our results suggest that ACR and GW4064 cooperatively inhibit RXRalpha phosphorylation, modulate the expression of FXR-regulated genes, thus resulting in the induction of apoptosis and the inhibition of growth in HCC cells. GW 4064 33-39 nuclear receptor subfamily 1 group H member 4 Homo sapiens 115-118 23119029-5 2012 In contrast, FXR overexpression and activation with GW4064 attenuated cell proliferation by down-regulating EGFR (Tyr845) phosphorylation and ERK activation. GW 4064 52-58 nuclear receptor subfamily 1 group H member 4 Homo sapiens 13-16 22561792-8 2012 Lithocholic acid (LCA) (10 muM), chenodeoxycholic acid (CDCA) (10 muM), or GW4064 (0.1 muM) treatment increased reporter activity in a construct including the three motifs under FXR-expressing conditions whereas LCA and not CDCA or GW4064 treatment increased the reporter activity under pregnane X receptor (PXR)-expressing conditions. GW 4064 75-81 nuclear receptor subfamily 1 group H member 4 Homo sapiens 178-181 22800197-12 2012 In LS174T cells, GW4064-induced chemoresistance was seen only after being transfected with FXR+RXR, when BCRP, but not MRP2, was up-regulated. GW 4064 17-23 nuclear receptor subfamily 1 group H member 4 Homo sapiens 91-94 22732083-9 2012 While a synthetic ligand for farnesoid X receptor (FXR), GW4064, did not increase the transcriptional activation in HrRXR- or HrRXR/HrFXR-transfected HEK-293 cells, the ligand showed weak but significant activity for a single amino acid mutant of HrRXR ((Phe)231(Cys)) and HrFXR cotransfected cells. GW 4064 57-63 nuclear receptor subfamily 1 group H member 4 Homo sapiens 51-54 22583617-3 2012 We previously found that compounds based on GW4064, a representative farnesoid X receptor (FXR) agonist, enhanced E297G BSEP transport activity. GW 4064 44-50 nuclear receptor subfamily 1 group H member 4 Homo sapiens 91-94 22583617-4 2012 Here, we conducted a structure-activity relationship analysis of GW4064 derivatives aimed at separating E297G BSEP-function-promoting activity and FXR-agonistic activity. GW 4064 65-71 nuclear receptor subfamily 1 group H member 4 Homo sapiens 147-150 21660973-5 2011 We used a commercially available FXR agonist, GW4064, as a model compound to assess preclinical efficacy in two species (hamster and cynomolgus monkey). GW 4064 46-52 nuclear receptor subfamily 1 group H member 4 Homo sapiens 33-36 21957312-8 2011 Second, CDCA, deoxycholic acid (DCA), and other synthetic FXR agonists, such as GW4064, significantly reduced rotavirus replication in cell culture in a dose-dependent manner. GW 4064 80-86 nuclear receptor subfamily 1 group H member 4 Homo sapiens 58-61 21988803-6 2011 The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. GW 4064 68-74 nuclear receptor subfamily 1 group H member 4 Homo sapiens 4-7 21988803-6 2011 The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. GW 4064 68-74 nuclear receptor subfamily 1 group H member 4 Homo sapiens 56-59 21988803-6 2011 The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. GW 4064 68-74 nuclear receptor subfamily 1 group H member 4 Homo sapiens 56-59 21988803-7 2011 More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. GW 4064 77-83 nuclear receptor subfamily 1 group H member 4 Homo sapiens 65-68 21988803-13 2011 We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. GW 4064 31-37 nuclear receptor subfamily 1 group H member 4 Homo sapiens 19-22 21596890-6 2011 3-(2,6-Dichlorophenyl)-4-(3"-carboxy-2-chlorostilben-4-yl-)oxymethyl-5-isopropyl-isoxazole (GW4064), a synthetic FXR ligand, had similar effects. GW 4064 92-98 nuclear receptor subfamily 1 group H member 4 Homo sapiens 113-116 21499302-4 2011 In this study, we show that activation of farnesoid X receptor (FXR), by the primary bile acid chenodeoxycholic acid (CDCA) or the synthetic agonist GW4064, inhibited growth of Tam-resistant breast cancer cells (termed MCF-7 TR1), which was used as an in vitro model of acquired Tam resistance. GW 4064 149-155 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-67 21364590-6 2011 The function of FXR was studied by small interfering RNA and treatment with FXR antagonist guggulsterone and FXR agonist GW4064. GW 4064 121-127 nuclear receptor subfamily 1 group H member 4 Homo sapiens 16-19 21364590-10 2011 Moreover, GW4064-mediated FXR activation increased cell migration and invasion. GW 4064 10-16 nuclear receptor subfamily 1 group H member 4 Homo sapiens 26-29 21291553-6 2011 RESULTS: Tetraodon FXR has a ligand selectivity profile very similar to human FXR, with strong activation by the synthetic ligand GW4064 and by the primary bile acid chenodeoxycholic acid. GW 4064 130-136 nuclear receptor subfamily 1 group H member 4 Homo sapiens 78-81 21319191-8 2011 Treatment of mouse or human hepatocytes with a farnesoid X receptor (FXR) agonist GW4064 or bile acids induced hepatic Abcg5/g8 expression. GW 4064 82-88 nuclear receptor subfamily 1 group H member 4 Homo sapiens 69-72 21291553-6 2011 RESULTS: Tetraodon FXR has a ligand selectivity profile very similar to human FXR, with strong activation by the synthetic ligand GW4064 and by the primary bile acid chenodeoxycholic acid. GW 4064 130-136 nuclear receptor subfamily 1 group H member 4 Homo sapiens 19-22 20189675-10 2010 The FXR inducer GW4064 activated UGT1A3 transcription, and electrophoretic mobility shift assays identified UGT1A3 as a FXR target gene. GW 4064 16-22 nuclear receptor subfamily 1 group H member 4 Homo sapiens 4-7 21085652-5 2010 We report in this study that treatment of quiescent HSCs with GW4064, a synthetic FXR agonist, significantly inhibited the HSC transdifferentiation, which was associated with an inhibition of the upregulation of ET-1 expression. GW 4064 62-68 nuclear receptor subfamily 1 group H member 4 Homo sapiens 82-85 20189675-10 2010 The FXR inducer GW4064 activated UGT1A3 transcription, and electrophoretic mobility shift assays identified UGT1A3 as a FXR target gene. GW 4064 16-22 nuclear receptor subfamily 1 group H member 4 Homo sapiens 120-123 19608735-10 2009 In vitro experiments show reduced induction of mRNA expression of relevant genes upon chenodeoxycholic acid and a selective FXR agonist GW4064 stimulation in EFA-deficient Caco-2 cells. GW 4064 136-142 nuclear receptor subfamily 1 group H member 4 Homo sapiens 124-127 19586769-1 2009 Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. GW 4064 70-77 nuclear receptor subfamily 1 group H member 4 Homo sapiens 58-61 19410460-0 2009 Substituted isoxazole analogs of farnesoid X receptor (FXR) agonist GW4064. GW 4064 68-74 nuclear receptor subfamily 1 group H member 4 Homo sapiens 55-58 19228886-0 2009 Knockdown of ATP8B1 expression leads to specific downregulation of the bile acid sensor FXR in HepG2 cells: effect of the FXR agonist GW4064. GW 4064 134-140 nuclear receptor subfamily 1 group H member 4 Homo sapiens 122-125 19228886-9 2009 Treatment with the synthetic FXR agonist GW4064 was able to partially neutralize ATP8B1 siRNA-mediated FXR downregulation and fully counteract inhibition of FXR target genes. GW 4064 41-47 nuclear receptor subfamily 1 group H member 4 Homo sapiens 29-32 19228886-9 2009 Treatment with the synthetic FXR agonist GW4064 was able to partially neutralize ATP8B1 siRNA-mediated FXR downregulation and fully counteract inhibition of FXR target genes. GW 4064 41-47 nuclear receptor subfamily 1 group H member 4 Homo sapiens 103-106 19228886-9 2009 Treatment with the synthetic FXR agonist GW4064 was able to partially neutralize ATP8B1 siRNA-mediated FXR downregulation and fully counteract inhibition of FXR target genes. GW 4064 41-47 nuclear receptor subfamily 1 group H member 4 Homo sapiens 103-106 19118524-3 2009 In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. GW 4064 73-79 nuclear receptor subfamily 1 group H member 4 Homo sapiens 44-47 19328688-0 2009 Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist. GW 4064 38-44 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-67 19328688-1 2009 According to the docking studies and the analysis of a co-crystal structure of GW4064 with FXR, a series of 3-aryl heterocyclic isoxazole analogs were designed and synthesized. GW 4064 79-85 nuclear receptor subfamily 1 group H member 4 Homo sapiens 91-94 18298956-4 2008 Moreover, activation of the BA-activated farnesoid X receptor (FXR) by its synthetic specific agonist GW4064 also decreased PCSK9 expression. GW 4064 102-108 nuclear receptor subfamily 1 group H member 4 Homo sapiens 41-61 19085950-3 2009 Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. GW 4064 81-87 nuclear receptor subfamily 1 group H member 4 Homo sapiens 37-57 19085950-3 2009 Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. GW 4064 81-87 nuclear receptor subfamily 1 group H member 4 Homo sapiens 59-62 18755856-1 2008 The farnesoid X receptor (FXR, NR1H4) belongs to the nuclear receptor superfamily and is activated by bile acids such as chenodeoxycholic acid, or synthetic ligands such as GW4064. GW 4064 173-179 nuclear receptor subfamily 1 group H member 4 Homo sapiens 26-29 18755856-1 2008 The farnesoid X receptor (FXR, NR1H4) belongs to the nuclear receptor superfamily and is activated by bile acids such as chenodeoxycholic acid, or synthetic ligands such as GW4064. GW 4064 173-179 nuclear receptor subfamily 1 group H member 4 Homo sapiens 31-36 18436567-4 2008 Two FXR ligands, chenodeoxycholic acid (CDCA) and GW4064, rescued HepG2 cells from serum deprivation-induced apoptosis in a dose-dependent manner. GW 4064 50-56 nuclear receptor subfamily 1 group H member 4 Homo sapiens 4-7 18298956-4 2008 Moreover, activation of the BA-activated farnesoid X receptor (FXR) by its synthetic specific agonist GW4064 also decreased PCSK9 expression. GW 4064 102-108 nuclear receptor subfamily 1 group H member 4 Homo sapiens 63-66 18029909-4 2007 METHODS AND RESULTS: The FXR target gene, small heterodimer partner (SHP), was induced in vascular smooth muscle cells after treatment with synthetic FXR ligands, GW4064, or 6alpha-ethyl-chenodeoxycholic acid. GW 4064 163-169 nuclear receptor subfamily 1 group H member 4 Homo sapiens 25-28 17988216-5 2008 In the present study, we report the expression of FXR in normal and cancer prostate epithelial cells, and we demonstrate that its activation by chenodeoxycholic acid or GW4064 negatively interferes with the levels of UGT2B15 and UGT2B17 mRNA and protein in prostate cancer LNCaP cells. GW 4064 169-175 nuclear receptor subfamily 1 group H member 4 Homo sapiens 50-53 16037943-7 2005 In these cells, the FXR pharmacological agonist GW4064 upregulated VPAC1 expression in a dose-dependent manner, and this effect was antagonized by the RXRalpha ligand, 9-cis retinoic acid. GW 4064 48-54 nuclear receptor subfamily 1 group H member 4 Homo sapiens 20-23 17047076-6 2006 At lower concentrations that had no direct effect on viability, the FXR agonist GW4064 induced expression of mRNA for the FXR target genes, small heterodimer partner (SHP), intestinal bile acid binding protein, and multidrug resistance-associated protein 2 (MRP-2), and repressed the expression of the SHP target gene aromatase. GW 4064 80-86 nuclear receptor subfamily 1 group H member 4 Homo sapiens 68-71 17047076-6 2006 At lower concentrations that had no direct effect on viability, the FXR agonist GW4064 induced expression of mRNA for the FXR target genes, small heterodimer partner (SHP), intestinal bile acid binding protein, and multidrug resistance-associated protein 2 (MRP-2), and repressed the expression of the SHP target gene aromatase. GW 4064 80-86 nuclear receptor subfamily 1 group H member 4 Homo sapiens 122-125 16946559-9 2006 Human SULT2A1 protein and mRNA levels were decreased in HepG2 cells treated with the FXR agonists, CDCA or GW4064 in dose-dependent manners, although SHP mRNA levels were increased. GW 4064 107-113 nuclear receptor subfamily 1 group H member 4 Homo sapiens 85-88 16012168-4 2005 AlphaA-crystallin was identified in a microarray screen as one of the most highly induced genes after treatment of HepG2 cells with the synthetic FXR ligand GW4064. GW 4064 157-163 nuclear receptor subfamily 1 group H member 4 Homo sapiens 146-149 15817812-5 2005 In addition, ICAM-1 and SHP mRNA levels were also induced in primary human hepatocytes when treated with chenodeoxycholic acid or GW4064, a FXR-selective agonist. GW 4064 130-136 nuclear receptor subfamily 1 group H member 4 Homo sapiens 140-143 15817812-7 2005 Both ICAM-1 and SHP expression were induced in a dose- and time-dependent manner by treatment with the FXR-selective agonist GW4064. GW 4064 125-131 nuclear receptor subfamily 1 group H member 4 Homo sapiens 103-106 15817812-8 2005 Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. GW 4064 37-43 nuclear receptor subfamily 1 group H member 4 Homo sapiens 65-68 15817812-8 2005 Moreover, the induction of ICAM-1 by GW4064 was inhibited by the FXR antagonist guggulsterone or with transfection of FXR siRNA. GW 4064 37-43 nuclear receptor subfamily 1 group H member 4 Homo sapiens 118-121 15342685-5 2004 The nonsteroidal synthetic FXR agonist GW4064 also decreases HL mRNA levels in HepG2 cells and in primary human hepatocytes. GW 4064 39-45 nuclear receptor subfamily 1 group H member 4 Homo sapiens 27-30 15692145-8 2005 Treatment of Huh7 cells with CDCA or the synthetic farnesoid X receptor (FXR) agonist GW4064 decreased mRNA and protein levels and also nuclear binding activity of HNF-4 alpha. GW 4064 86-92 nuclear receptor subfamily 1 group H member 4 Homo sapiens 73-76 15342685-7 2004 In addition, FXR-specific gene silencing using small interfering RNAs demonstrated that CDCA- and GW4064-mediated downregulation of HL transcript levels occurs via an FXR-dependent mechanism. GW 4064 98-104 nuclear receptor subfamily 1 group H member 4 Homo sapiens 13-16 15342685-7 2004 In addition, FXR-specific gene silencing using small interfering RNAs demonstrated that CDCA- and GW4064-mediated downregulation of HL transcript levels occurs via an FXR-dependent mechanism. GW 4064 98-104 nuclear receptor subfamily 1 group H member 4 Homo sapiens 167-170 14684751-6 2004 Similar results were also obtained from a glutathione S-transferase pull-down assay in which only CDCA and the synthetic FXR agonist GW4064 significantly increased the interaction of SRC-1 with FXR. GW 4064 133-139 nuclear receptor subfamily 1 group H member 4 Homo sapiens 121-124 15309887-6 2004 Intestinal bile acid binding protein was activated by chenodeoxycholic acid and the synthetic FXR agonist GW4064 in Caco-2 and HT-29 but not in SW cells unless FXR was transfected. GW 4064 106-112 nuclear receptor subfamily 1 group H member 4 Homo sapiens 94-97 14684751-6 2004 Similar results were also obtained from a glutathione S-transferase pull-down assay in which only CDCA and the synthetic FXR agonist GW4064 significantly increased the interaction of SRC-1 with FXR. GW 4064 133-139 nuclear receptor subfamily 1 group H member 4 Homo sapiens 194-197 12052824-11 2002 In an in vitro co-activator association assay, LCA decreased CDCA- and GW4064-induced FXR activation with an IC(50) of 1 microm. GW 4064 71-77 nuclear receptor subfamily 1 group H member 4 Homo sapiens 86-89 12761213-5 2003 In primary human hepatocytes, both the endogenous FXR agonist chenodeoxycholate and synthetic FXR agonist GW4064 increased kininogen mRNA with a maximum induction of 8-10-fold. GW 4064 106-112 nuclear receptor subfamily 1 group H member 4 Homo sapiens 94-97 12660231-2 2003 Treatment of human hepatocytes with either naturally occurring (chenodeoxycholic acid) or synthetic (GW4064) FXR ligands resulted in both induction of SDC1 mRNA and enhanced binding, internalization, and degradation of low density lipoprotein. GW 4064 101-107 nuclear receptor subfamily 1 group H member 4 Homo sapiens 109-112 12554753-6 2003 Incubation of human hepatoma HepG2 cells with the natural FXR ligand chenodeoxycholic acid (CDCA) as well as with the nonsteroidal FXR agonist GW4064 resulted in a significant induction of PPARalpha mRNA levels. GW 4064 143-149 nuclear receptor subfamily 1 group H member 4 Homo sapiens 131-134 14527955-5 2003 In FXR trans-activation assays, both the endogenous FXR agonist chenodeoxycholate and the synthetic agonist GW4064 activated the MDR3 promoter. GW 4064 108-114 nuclear receptor subfamily 1 group H member 4 Homo sapiens 3-6 12891557-7 2003 Incubation of human primary hepatocytes and HepG2 cells with bile acids or the nonsteroidal synthetic FXR agonist GW4064 resulted in a dose-dependent down-regulation of Apo CIII gene expression. GW 4064 114-120 nuclear receptor subfamily 1 group H member 4 Homo sapiens 102-105 12525500-5 2003 In HepG2 cells, in the presence of an FXR agonist such as chenodeoxycholate or GW4064, GS enhanced endogenous BSEP expression with a maximum induction of 400-500% that induced by an FXR agonist alone. GW 4064 79-85 nuclear receptor subfamily 1 group H member 4 Homo sapiens 38-41 12525500-5 2003 In HepG2 cells, in the presence of an FXR agonist such as chenodeoxycholate or GW4064, GS enhanced endogenous BSEP expression with a maximum induction of 400-500% that induced by an FXR agonist alone. GW 4064 79-85 nuclear receptor subfamily 1 group H member 4 Homo sapiens 182-185 12052824-6 2002 Both the endogenous FXR agonist chenodeoxycholate (CDCA) and synthetic FXR ligand GW4064 effectively increased BSEP mRNA in both cell types. GW 4064 82-88 nuclear receptor subfamily 1 group H member 4 Homo sapiens 71-74 12052824-12 2002 In HepG2 cells, LCA also effectively antagonized GW4064-enhanced FXR transactivation. GW 4064 49-55 nuclear receptor subfamily 1 group H member 4 Homo sapiens 65-68 11927623-9 2002 The nonsteroidal synthetic FXR agonist GW4064 likewise decreased apoA-I mRNA levels and promoter activity in HepG2 cells. GW 4064 39-45 nuclear receptor subfamily 1 group H member 4 Homo sapiens 27-30 34888230-6 2021 Importantly, FXR agonist (GW4064) can synergize with anti-PD-1 antibody (Ab) to inhibit HCC growth in tumor-bearing models. GW 4064 26-32 nuclear receptor subfamily 1 group H member 4 Homo sapiens 13-16 11607932-3 2001 GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor FXR (NR1H4). GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 88-91 11607932-3 2001 GW4064 is a potent and selective nonsteroidal ligand for the nuclear bile acid receptor FXR (NR1H4). GW 4064 0-6 nuclear receptor subfamily 1 group H member 4 Homo sapiens 93-98 11607932-4 2001 Using GW4064 as a chemical tool, we have identified genes regulated by FXR in the liver, including those involved in bile acid synthesis and transport. GW 4064 6-12 nuclear receptor subfamily 1 group H member 4 Homo sapiens 71-74 34998040-5 2022 Here we report the synthesis and characterization of compound HEC96719 a novel tricyclic FXR agonist based on a prior high-affinity nonsteroidal molecule GW4064. GW 4064 154-160 nuclear receptor subfamily 1 group H member 4 Homo sapiens 89-92 34145381-4 2021 HepG2 cells and primary hepatocytes were incubated with chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), ursodeoxycholic acid (UCDA), or the synthetic FXR agonist GW4064 for 24 h. MTT tests demonstrated cell viability throughout experiments. GW 4064 180-186 nuclear receptor subfamily 1 group H member 4 Homo sapiens 168-171 34145381-8 2021 Quantitative polymerase chain reaction revealed upregulation of FXR target genes only by CDCA and GW4064. GW 4064 98-104 nuclear receptor subfamily 1 group H member 4 Homo sapiens 64-67 34256254-5 2021 Thus, we decided to develop non-steroidal FXR agonists and discovered a series of novel FXR agonists which were synthesized from GW4064 by replacing the stilbene group with ketoxime ether. GW 4064 129-135 nuclear receptor subfamily 1 group H member 4 Homo sapiens 42-45 34256254-5 2021 Thus, we decided to develop non-steroidal FXR agonists and discovered a series of novel FXR agonists which were synthesized from GW4064 by replacing the stilbene group with ketoxime ether. GW 4064 129-135 nuclear receptor subfamily 1 group H member 4 Homo sapiens 88-91 34998040-6 2022 HEC96719 exhibits excellent potency superior to GW4064 and obeticholic acid in in vitro and in vivo assays of FXR activation. GW 4064 48-54 nuclear receptor subfamily 1 group H member 4 Homo sapiens 110-113