RN-18 is an inhibitor of HIV-1 viral infectivity factor (IC50: 6 μM in nonpermissive H9 cells).

Non-permissive H9 cells:6 μM (IC50)

RN-18 displays the greater potency (IC50=4.5 μM in CEM cells) and specificity (IC50>100 μM in MT4 cells) among the two compounds. RN-18 and RN-19 show effective 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 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 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. Reverse transcriptase activity in the nonpermissive H9 and CEM cells decreases substantially and in a dose-dependent manner in the presence of the inhibitor RN-18. RN-18 antagonizes the Vif function and inhibits HIV-1 replication only in the presence of A3G [1][2].