NBD-09027

NBD-09027 is a HIV-1 gp120 inhibitor. NBD-09027 blocks the gp120-CD4 interaction by binding to the Phe43 cavity of gp120, thereby inhibiting HIV-1-mediated cell fusion and the infectivity of multiple viral subtypes. NBD-09027 can be used in studies of human immunodeficiency virus type 1 infection^[1][2][3]. In Vitro:NBD-09027 (3 h) inhibits HIV-1-mediated cell-cell fusion between HIV-1_IIIB-infected H9 cells and MT-2 cells, with an IC₅₀ of 2.3 μM^[1].
NBD-09027 (1 h) blocks the binding of CD4 to recombinant HIV-1_IIIB gp120, with an IC₅₀ of 6.2 μM^[1].
NBD-09027 inhibits the infection of U87-CD4-CCR5 cells by R5-tropic NL4-3-ADA-Luc pseudovirus (IC₅₀ = 9.1 μM) and the infection of U87-CD4-CXCR4 cells by X4-tropic NL4-3-HXB2-Luc pseudovirus (IC₅₀ = 8.6 μM)^[1].
NBD-09027 potently and selectively inhibits the infection of TZM-bl cells by multiple HIV-1 Env pseudotyped reference viruses of subtypes A, A/D, A2/D, A/E, A/G, B, C, and D, with IC₅₀ values ranging from 0.7 μM to > 21 μM and a CC₅₀ value of > 32 μM^[1].
NBD-09027 (30-55 μM; for up to 9 weeks) selects drug-resistant viruses carrying the NN301-302KI, K432R, and V782L mutations during serial passage of NL4-3 HIV-1 in Jurkat cells^[1].
NBD-09027 (4-7 days) inhibits the laboratory-adapted HIV-1 isolate in MT-2 cells with an IC₅₀ range of 4-35.8 μM, but exhibits only weak or no activity against primary HIV-1 isolates of subtype C and group O in PBMCs^[2].
NBD-09027 (4 h) exhibits weak inhibitory activity against the cell-to-cell transmission of CXCR4-tropic HIV-1 in GHOST (3) X4/R5 cells, with an IC₅₀ of approximately 60 μM, and shows no inhibitory activity against the cell-to-cell transmission of CCR5-tropic HIV-1^[2].
NBD-09027 (10-50 μM) dose-dependently inhibits the infectivity of CD4-dependent HIV-1 NL4-3-ADA-Luc in CD4-positive Cf2Th-CD4-CCR5 cells, with more potent inhibitory effects at higher concentrations up to 50 μM; meanwhile, it dose-dependently enhances the infectivity of CD4-independent HIV-1 NL4-3-ADA-N197S-Luc in CD4-negative Cf2Th-CCR5 cells^[1].
NBD-09027 (10-50 μM) inhibits the infectivity of ENV-pseudotyped HIV-1 strains NIH #11313, NIH #11906, NIH #11601, and NIH #11890 in a dose-dependent manner, and its inhibitory effect increases when the concentration is elevated to 50 μM^[1].
NBD-09027 (compound 6) exhibits consistently enhanced anti-HIV-1 activity against the vast majority of HIV-1 subtypes represented by a panel of 53 reference Env pseudoviruses^[1].
NBD-09027 significantly reduces the CD4 agonist activity. Drug resistance selection confirms that it binds to the CD4 binding site on HIV-1 gp120, and mutations are detected at concentrations of 44 μM and 55 μM ^[1].