[CAS NO. 192725-17-0]  Lopinavir (ABT-378)

Lopinavir binds to mutant HIV protease (V82A, V82F and V82T) with Ki of 4.9 pM, 3.7 pM and 3.6 pM, respectively. Lopinavir inhibits 93% of wild-type HIV protease activity at 0.5 nM. Lopinavir inhibits HIV protease activity in the absence and presence of 50% HS with EC50 of 17 nM and 102 nM, respectively, in MT4 cells. Lopinavir is converted to several metabolites in an NADPH-dependent manner in liver microsomes with the primary metabolites M-3 and M-4. Lopinavir is a potent inhibitor of Rh123 efflux in Caco-2 monolayers with IC50 of 1.7 mM. Lopinavir exposure (72 hours) in LS 180V cells reduces the content of intracellular Rh123. Lopinavir induces P-glycoprotein immunoreactive protein and messenger RNA levels in LS 180V cells. Lopinavir inhibits subtype C clone C6 with IC50 of 9.4 nM. Lopinavir inhibits CYP3A with IC50 of 7.3 mM in human liver microsomes, while produces negligible or weak inhibition of human CYP1A2, 2B6, 2C9, 2C19 and 2D6.