NSC727447

NSC727447 is a vinyl urea-based allosteric inhibitor of HIV reverse transcriptase-associated RNase H with IC₅₀ values of 2.0 μM and 2.5 μM against HIV-1 and HIV-2 RNase H, respectively, and IC₅₀ values of 100 μM and 10.6 μM against Escherichia coli and human RNase H, respectively. NSC727447 exerts allosteric inhibitory effects mainly by interacting with the region adjacent to α-helix I in the thumb subdomain of the p51 subunit of HIV-1 reverse transcriptase. Cys280, Lys281 and the RNase H primer grip region are involved in its action, and it may inhibit the catalytic activity of RNase H by altering the positioning of nucleic acid substrates or the geometry of the RNase H active site. NSC727447 can be used in studies related to HIV infection, the function of HIV reverse transcriptase RNase H, and allosteric inhibition mechanisms^[1][2]. In Vitro:NSC727447 inhibits the RT-associated RNase H activities of HIV-1 and HIV-2 with IC₅₀ values of 2.0 μM and 2.5 μM, respectively, while its IC₅₀ values against E. coli and human RNase H are 100 μM and 10.6 μM, respectively^[1].
NSC727447 (50 μM) does not inhibit the RNA-dependent DNA polymerase and pyrophosphorolysis activities of HIV-1 RT, demonstrating preferential inhibitory activity against RNase H function^[1].
NSC727447 (0-16 μM) exhibits mutually exclusive inhibition with α-thujaplicinol, an active-site RNase H inhibitor, suggesting that NSC727447 modulates RNase H activity via a mechanism distinct from direct metal chelation^[1].
NSC727447 (37 °C; 10 min) inhibits wild-type HIV-1 RT RNase H activity with an IC₅₀ of 1.20 μM, while the p51 thumb C280A mutation reduces its inhibitory sensitivity by approximately 3-fold, supporting the involvement of the p51 thumb in the allosteric action of NSC727447^[2].