PF-3450074

PF-3450074 (PF-74) is a specifical inhibitor of?HIV-1 capsid protein (CA) and displays a broad-spectrum inhibition of HIV isolates with submicromolar potency (EC₅₀=8-640 nM). PF-3450074 (PF-74) acts at an early stage of HIV-1 infection, inhibits viral replication by directly competing with the binding of CPSF6 and NUP153, and blocks the uncoating, assembly, and the reverse transcription steps of the viral life cycle^[1][2]. CPSF6: nuclear host factors cleavage and polyadenylation specific factor 6; NUP153: nucleoporin 153. In Vitro: PF-3450074 (PF-74) exhibits anti-viral activities against HIV wild type NL4-3 and HIV T107N mutant with EC₅₀ values of 0.72 μM and 4.5μM, respectively^[1].
PF-3450074 (PF-74) displays a good potency in primary human peripheral blood mononuclear cells (PBMCs), inhibits HIV-193RW025, HIV-1JR-CSF and HIV-193MW965 with IC₅₀ values of 1.5 ± 0.9 μM; 0.6 ± 0.20 μM; and 0.6 ± 0.10 μM, respectively. This compound shows Median IC₅₀?and CC₅₀?values of 0.9 ± 0.5 μM and 90.5 ± 5.9 μM, respectively^[1].
The KD?for the interaction between?PF-74?and the CA hexamer, derived in the same manner as for NUP153, is determined to be 176 ± 78 nM^[1].
PF-3450074 (PF-74) (10 μM; 8 hours) results in a marked reduction in late products of reverse transcription in HeLa-P4 cells with DNase I-treated stocks of Env-defective HIV-1 (R9.Env^-)^[2].