Doravirine

Doravirine (MK-1439) is a highly specific HIV-1 nonnucleoside reverse transcriptase inhibitor with IC₅₀s of 4.5 nM, 5.5 nM and 6.1 nM against the wild type and K103N and Y181C reverse transcriptase mutants, respectively^[1]. IC50 & Target:IC50: 4.5 nM (wild type reverse transcriptase); 5.5 nM ( K103N reverse transcriptase); 6.1 nM (Y181C reverse transcriptase)^[1] 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)^[1]. 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 C_max^[2].