Doravirine (MK-1439) is a highly specific HIV-1 nonnucleoside reverse transcriptase inhibitor with IC50s of 12, 9.7 and 9.7nM against the wild type and K103N and Y181C reverse transcriptase mutants, respectively. Selectivity and cytotoxicity studies confirmed that Doravirine is a highly specific nonnucleoside reverse transcriptase inhibitor 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[3]. Doravirine exhibits similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses). 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[4].
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