RN-18

RN-18 is a HIV-1 viral infectivity factor (HIV-1 Vif) inhibitor with an IC₅₀ of 6 μM in nonpermissive H9 cells. IC50 & Target: IC50: 6 μM (nonpermissive H9 cell)^[1] In Vitro: RN-18 and RN-19 exhibits potent antiviral activity in the nonpermissive H9 and CEM cells but not in MT4 or CEM-SS cells, confirming that the antiviral activity was Vif specific. RN-18 shows the greater potency (IC₅₀=4.5 μM in CEM cells) and specificity (IC₅₀>100 μM in MT4 cells) among the two compounds^[1]. In the presence of the inhibitor, RN-18, reverse transcriptase activity in the nonpermissive H9 and CEM cells decreases substantially and in a dose-dependent manner. RN-18 also exhibits antiviral activity in CEM-SS modified to stably express A3G but does not exhibit antiviral activity in the parental CEM-SS cell line. RN-18 antagonizes Vif function and inhibits HIV-1 replication only in the presence of A3G. RN-18 increases cellular A3G levels in a Vif-dependent manner and increases A3G incorporation into virions without inhibiting general proteasome-mediated protein degradation. RN-18 enhances Vif degradation only in the presence of A3G, reduces viral infectivity by increasing A3G incorporation into virions and enhances cytidine deamination of the viral genome^[2].