Doravirine

Doravirine (MK-1439, MK1439) is a novel, highly specific HIV-1 nonnucleoside reverse transcriptase inhibitor (NNRTI) with IC50 of 12, 9.7, and 9.7 nM against WT, K103N, and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay; shows excellent potency in suppressing the replication of WT virus with EC95 of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively.HIV Infection Phase 3 Clinical(In Vitro):Selectivity and cytotoxicity studies confirmed that Doravirine is a highly specific nonnucleoside reverse transcriptase inhibitors with minimum off-target activities. In the presence of 50% normal human serum (NHS), Doravirine shows excellent potency in suppressing the replication of WT virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC9595 of 43, 27, and 55 nM, respectively. Doravirine exhibits similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses).(In Vivo):Administration of 50 mg Doravirine with a high-fat meal is associated with slight elevations in AUC time zero to infinity and C24 h with no change in Cmax.