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

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. 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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Mohammed I, et al. SAR and Lead Optimization of an HIV-1 Vif-APOBEC3G Axis Inhibitor. ACS Med Chem Lett. 2012 Jun 14;3(6):465-469.  [Content Brief]

  . Nathans R, et al. Small-molecule inhibition of HIV-1 Vif. Nat Biotechnol. 2008 Oct;26(10):1187-92.  [Content Brief]