Sequential metabolism of AMG 487, a novel CXCR3 antagonist, results in formation of quinone reactive metabolites that covalently modify CYP3A4 Cys239 and cause time-dependent inhibition of the enzyme

Drug Metabolism and Disposition

Volumn 40, Issue 7, 2012, Pages 1429-1440

  Henne, Kirk R ^a   Tran, Thuy B ^a   VandenBrink, Brooke M ^a   Rock, Dan A ^a   Aidasani, Divesh K ^a   Subramanian, Raju ^a   Mason, Andrew K ^b   Stresser, David M ^b   Teffera, Yohannes ^a   Wong, Simon G ^a   Johnson, Michael G ^a   Chen, Xiaoqi ^a   Tonn, George R ^a   Wong, Bradley K ^a  

^a AMGEN INC   (United States)

^b BD Gentest Contract Research Services   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMG 487; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CXCR3; CHEMOKINE RECEPTOR CXCR3 ANTAGONIST; CYTOCHROME P450 3A4; GLUTATHIONE; MIDAZOLAM; OXYGEN; QUINONE DERIVATIVE; TESTOSTERONE; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME INHIBITION; HUMAN; IC 50; IN VITRO STUDY; MAXIMUM PLASMA CONCENTRATION; METABOLITE; PRIORITY JOURNAL; PROTEIN DEGRADATION;

ACETAMIDES; BIOTRANSFORMATION; CYTOCHROME P-450 CYP3A; HUMANS; METABOLIC NETWORKS AND PATHWAYS; MICROSOMES, LIVER; MIDAZOLAM; OXYGEN; PROTEOLYSIS; PYRIMIDINONES; QUINONES; RECEPTORS, CXCR3; TESTOSTERONE;

EID: 84862674138     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.045708     Document Type: Article

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