HIV-1 integrase inhibitor is useful for anti-HIV, with IC50 value of 0.33 µM, which can target HIV-1 integrase and depress the activity in the treatment of HIV infection, AIDS, and other similar diseases characterized by integration of a retroviral genome into a host chromosome.
Elvitegravir (also known as GS-9137 or JTK-303), a monoketo acid modified from the distinct diketo acid moiety (DKA) motif, is a potent inhibitor of human immunodeficiency virus type I (HIV-1) integrase, an enzyme integrating the viral DNA into the cellular DNA of the host during HIV replication.
Fluorouracil (Adrucil), a heterocyclic aromatic organic compound, is a potent anticancer agent widely used for the treatment of solid tumors, including breast cancer, ovarian cancer, head and neck cancer, and colon cancer. As an analogue of uracil, fluorouracil has a fluorine atom replacing the hydrogen atom at the C-5 position.
MK-2048 is a second generation inhibitor of HIV-1 integrase with IC50 values of 0.075 μM and 0.08 μM for subtype B and subtype C integrase, respectively. Integration of viral cDNA into the host genome is one of the definitive features of retrovirus replication. Integrase inhibitors are active against both B and non-B subtypes in therapy. Subtype C variants are responsible for approximately 50% of infections worldwide, mostly in Sub-Saharan Africa and India. After viral entry and reverse transcription, reverse-transcribed double-stranded blunt-ended DNA is incorporated into the host cell genome through two catalytic activities mediated by integrase. MK-2048 could inhibit the strand transfer process catalyzed by integrase. The inhibition activity of MK-2048 against integrase was evaluated by means of purified recombinant subtype B and C integrase enzymes, which were obtained and amplified from viruses in long-term infected patients. Purified recombinant subtype B and C integrase enzymes were incubated with increasing concentrations of MK-2048 and corresponding templates. MK-2048 possesses inhibition activities for strand transfer against subtype B and C enzymes, whose IC50 values were 0.075 μM and 0.08 μM, respectively. Disintegration was inhibited by high concentrations of MK-2048 to a comparable extent with both subtype B and C enzymes. Inhibition of replication by MK-2048 was also evaluated in cell culture based assays using cord blood mononuclear cells. EC50 for subtype B viruses varies from 0.0003 μM to 0.0148 μM and 0.0007 μM to 0.0033 μM for subtype C viruses. References: 1.Bar-Magen T, Sloan R D, Faltenbacher V H, et al. Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes[J]. Retrovirology, 2009, 6(1): 103.