tcsc2252 Nevirapine

Nevirapine is a non-nucleoside inhibitor of HIV-1 reverse transcriptase used to treat and prevent HIV/AIDS; with a K_i of 270 μM.

IC50 & Target: Ki: 270 μM (HIV-1 reverse transcriptase)^[1]

In Vitro: Nevirapine itself is an inhibitor of only CYP3A4 at concentrations that are well above those of therapeutic relevance (K_i=270 μM)^[1]. Nevirapine has been used as a re-differentiation agent to treat cancers in several human cancer models. At all doses (100, 200, 350, 500 μM) tested, nevirapine significantly inhibits cell proliferation after 48 h treatment. At high dose (500 μM), nevirapine significantly increases the percentage of apoptotic cells compared with control^[2]. Nevirapine is a potent and selective inhibitor (IC₅₀=10-100 nM) of the replication of a wide variety of HIV-1 strains in several cellular assays^[3].

In Vivo: Nevirapine is available for use in combination with nucleoside HIV-1 reverse transcriptase inhibitors (e.g., zidovudine, didanosine, etc.). Nevirapine has received FDA approval for use in combination with HIV-1 protease inhibitors (e.g., saquinavir, ritonavir, indinavir, etc.). In humans, nevirapine is eliminated primarily in the urine as glucuronide conjugates of 2-, 3-, 8-, and 12-hydroxynevirapine^[1]. Nevirapine is completely absorbed in both sexes of mouse, rat, rabbit, monkey, and chimpanzee. Nevirapine is extensively metabolized in both sexes of all animal species studied^[4]. Nevirapine (9 mg/kg, 18 mg/kg and 36 mg/kg) shows significant reduction in ulcer severity score and ulcer index as compared to the control^[5]