MK-0536

MK-0536 is a potent HIV-1 integrase inhibitor that effectively suppresses the replication of wild-type viruses. It retains significant antiviral activity against key resistant mutants such as Y143R and N155H, without exhibiting toxicity to uninfected cells. MK-0536 selectively blocks the integrase strand transfer reaction by chelating magnesium ions at the active site and interacting with viral DNA and enzyme residues. This compound is useful for studying the mechanisms of HIV infection.

MK-0536, with a concentration range of 0.6 nM to 37 μM over a 2-hour period, exhibits high sensitivity to wild-type HIV-1 integrase, inhibiting strand transfer with an IC50 of 33 nM and 3'-processing activity with an IC50 of 5.8 μM. It is also highly sensitive to the Y143R variant of HIV-1 integrase, effectively inhibiting strand transfer (IC50 of 9.5 nM) and 3'-processing (IC50 of 1.4 μM). Against the N155H variant, MK-0536 inhibits strand transfer with an IC50 of 40 nM and 3'-processing with an IC50 of 3.9 μM. For the G140S-Q148H variant, MK-0536 shows reduced activity, inhibiting strand transfer (IC50 of 237 nM) and 3'-processing (IC50 of 8.3 μM). Additionally, MK-0536 inhibits the replication of wild-type HIV-1 in HOS cells with an EC50 of 17 nM, and it is non-cytotoxic to HeLa cells at concentrations up to 333 μM.