PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9241661-0 1997 Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Cyclophosphamide 118-134 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 48-55 9241661-0 1997 Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Cyclophosphamide 118-134 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 74-80 9241661-0 1997 Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Ifosfamide 139-149 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 48-55 9241661-0 1997 Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Ifosfamide 139-149 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 74-80 9241661-1 1997 Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic activity. Cyclophosphamide 0-16 cytochrome P450 family 4 subfamily F member 3 Homo sapiens 89-104 9241661-1 1997 Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic activity. Cyclophosphamide 0-16 cytochrome P450 family 4 subfamily F member 3 Homo sapiens 106-109 9241661-1 1997 Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic activity. Ifosfamide 21-31 cytochrome P450 family 4 subfamily F member 3 Homo sapiens 89-104 9241661-1 1997 Cyclophosphamide and ifosfamide are alkylating agent prodrugs that require activation by cytochrome P450 (CYP) to manifest their cancer chemotherapeutic activity. Ifosfamide 21-31 cytochrome P450 family 4 subfamily F member 3 Homo sapiens 106-109 9241661-2 1997 The present study investigates the activity of four individual human CYP2C enzymes and their allelic variants in cyclophosphamide and ifosfamide activation as an initial attempt to gain insight into the underlying basis for the large interpatient differences in the clinical pharmacokinetics and metabolism of these anticancer drugs. Cyclophosphamide 113-129 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 69-74 9241661-2 1997 The present study investigates the activity of four individual human CYP2C enzymes and their allelic variants in cyclophosphamide and ifosfamide activation as an initial attempt to gain insight into the underlying basis for the large interpatient differences in the clinical pharmacokinetics and metabolism of these anticancer drugs. Ifosfamide 134-144 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 69-74 9241661-3 1997 Recombinant CYP2C8, CYP2C19, two allelic variants of CYP2C18, and six variants of CYP2C9 expressed in a yeast cDNA expression system were each enzymatically active, as judged by the ability of the isolated microsomes to catalyse 7-ethoxycoumarin O-deethylation after reconstitution with purified NADPH-cytochrome P450 reductase and cytochrome b5. 3-ethoxychromen-2-one 231-245 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 12-18 9241661-3 1997 Recombinant CYP2C8, CYP2C19, two allelic variants of CYP2C18, and six variants of CYP2C9 expressed in a yeast cDNA expression system were each enzymatically active, as judged by the ability of the isolated microsomes to catalyse 7-ethoxycoumarin O-deethylation after reconstitution with purified NADPH-cytochrome P450 reductase and cytochrome b5. 3-ethoxychromen-2-one 231-245 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 82-88 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 36-43 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 84-90 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 92-99 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 104-110 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 170-177 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 183-190 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 196-202 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Cyclophosphamide 5-21 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 208-214 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Ifosfamide 135-145 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 36-43 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Ifosfamide 135-145 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 84-90 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Ifosfamide 135-145 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 92-99 9241661-4 1997 With cyclophosphamide as substrate, CYP2C19 had the lowest apparent Km, followed by CYP2C9, CYP2C18 and CYP2C8, whereas in the case of ifosfamide, the rank order was: Km CYP2C19 < CYP2C18 < CYP2C9 < CYP2C8. Ifosfamide 135-145 cytochrome P450 family 2 subfamily C member 8 Homo sapiens 104-110 9241661-5 1997 CYP2C18 had the highest in vitro intrinsic clearance/catalytic efficiency (apparent Vmax/Km) in cyclophosphamide and ifosfamide activation, followed by 2C19 > 2C9 approximately 2C8. Cyclophosphamide 96-112 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 0-7 9241661-5 1997 CYP2C18 had the highest in vitro intrinsic clearance/catalytic efficiency (apparent Vmax/Km) in cyclophosphamide and ifosfamide activation, followed by 2C19 > 2C9 approximately 2C8. Ifosfamide 117-127 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 0-7 9241661-6 1997 Examination of a panel of CYP2C allelic variants revealed that CYP2C18-Thr385 had both a higher Vmax and a higher apparent Km toward cyclophosphamide than CYP2C18-Met385 with no difference in catalytic efficiency, whereas with ifosfamide the Thr385 allele exhibited a strikingly lower apparent Km resulting in a six-fold higher catalytic efficiency. Cyclophosphamide 133-149 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 63-70 9241661-6 1997 Examination of a panel of CYP2C allelic variants revealed that CYP2C18-Thr385 had both a higher Vmax and a higher apparent Km toward cyclophosphamide than CYP2C18-Met385 with no difference in catalytic efficiency, whereas with ifosfamide the Thr385 allele exhibited a strikingly lower apparent Km resulting in a six-fold higher catalytic efficiency. Ifosfamide 227-237 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 63-70 9241661-7 1997 In the case of CYP2C9, a Ile359 to Leu mutation associated with poor metabolism of the hypoglycemic drug tolbutamide decreased catalytic efficiency toward cyclophosphamide by increasing the apparent Km, whereas the same mutation reduced the efficiency of this P450 toward ifosfamide by decreasing the Vmax. Tolbutamide 105-116 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 9241661-7 1997 In the case of CYP2C9, a Ile359 to Leu mutation associated with poor metabolism of the hypoglycemic drug tolbutamide decreased catalytic efficiency toward cyclophosphamide by increasing the apparent Km, whereas the same mutation reduced the efficiency of this P450 toward ifosfamide by decreasing the Vmax. Cyclophosphamide 155-171 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 9241661-7 1997 In the case of CYP2C9, a Ile359 to Leu mutation associated with poor metabolism of the hypoglycemic drug tolbutamide decreased catalytic efficiency toward cyclophosphamide by increasing the apparent Km, whereas the same mutation reduced the efficiency of this P450 toward ifosfamide by decreasing the Vmax. Ifosfamide 272-282 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 15-21 9241661-8 1997 Substitution of CYP2C9-Gly417 by Asp resulted in a two-fold lower catalytic efficiency for cyclophosphamide metabolism but a three-fold higher efficiency for ifosfamide metabolism. Cyclophosphamide 91-107 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 9241661-8 1997 Substitution of CYP2C9-Gly417 by Asp resulted in a two-fold lower catalytic efficiency for cyclophosphamide metabolism but a three-fold higher efficiency for ifosfamide metabolism. Ifosfamide 158-168 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 16-22 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Cyclophosphamide 73-89 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 19-26 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Cyclophosphamide 73-89 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 31-37 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Cyclophosphamide 73-89 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 19-24 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Cyclophosphamide 73-89 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 307-313 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Cyclophosphamide 73-89 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 318-325 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Ifosfamide 94-104 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 19-26 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Ifosfamide 94-104 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 31-37 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Ifosfamide 94-104 cytochrome P450 family 2 subfamily C member 19 Homo sapiens 19-24 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Ifosfamide 94-104 cytochrome P450 family 2 subfamily C member 9 Homo sapiens 307-313 9241661-11 1997 Thus (a) wild type CYP2C19 and CYP2C9 are relatively low Km catalysts of cyclophosphamide and ifosfamide activation, and (b) all four human CYP2C enzymes activate these two anticancer prodrugs with varying efficiencies and with striking differences among naturally occurring allelic variants in the case of CYP2C9 and CYP2C18. Ifosfamide 94-104 cytochrome P450 family 2 subfamily C member 18 Homo sapiens 318-325