Title : In vitro characterization of the drug-drug interaction potential of catabolites of antibody-maytansinoid conjugates.

Pub. Date : 2012 Oct

PMID : 22752008






3 Functional Relationships(s)
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1 Studies with recombinant human cytochromes P450 (P450s) indicate CYP2D6, CYP3A4, and CYP3A5 are the primary isoforms responsible for the oxidative metabolism of DM1, (S)-methyl-DM1, and DM4. Maytansine cytochrome P450 family 3 subfamily A member 4 Homo sapiens
2 DM1 and DM4 inactivated CYP3A from human liver microsomes with K(i)/k(inact) values of 4.8 +- 0.9 muM/0.035 +- 0.002 min(-1) and 3.3 +- 0.2 muM/0.114 +- 0.002 min(-1), respectively. Maytansine cytochrome P450 family 3 subfamily A member 4 Homo sapiens
3 DM1 and DM4 inactivated recombinant CYP3A4 with K(i)/k(inact) values of 3.4 +- 1.0 muM/0.058 +- 0.005 min(-1) and 1.4 +- 0.3 muM/0.117 +- 0.006 min(-1), respectively. Maytansine cytochrome P450 family 3 subfamily A member 4 Homo sapiens