| Description | PF-3450074 (PF-74) acts at an early stage of HIV-1 infection inhibits viral replication by directly competing with the binding of CPSF6 (nuclear host factors cleavage and polyadenylation specific factor 6) and NUP153 (nucleoporin 153), and blocks the uncoating, assembly, and the reverse transcription steps of the viral life cycle. PF-3450074 is a specifical inhibitor of HIV-1 capsid protein (CA) and shows a broad-spectrum inhibition of HIV isolates with submicromolar potency (EC50=8-640 nM). |
| In vitro | PF-3450074在原代人外周血单核细胞(PBMCs)中表现出良好的活性，对HIV-193RW025、HIV-1JR-CSF和HIV-193MW965的抑制作用达到IC50值分别为1.5 ± 0.9 μM、0.6 ± 0.20 μM和0.6 ± 0.10 μM。此化合物还展示了对HIV野生型NL4-3和HIV T107N突变体的抗病毒活性（EC50值分别为0.72 μM和4.5μM）。在使用DNase I处理过的Env缺陷HIV-1（R9.Env-）感染的HeLa-P4细胞中，PF-3450074（10 μM；8小时）显著降低了逆转录后期产品的水平。该化合物的中位IC50和CC50值分别为0.9 ± 0.5 μM和90.5 ± 5.9 μM。与NUP153相似，通过相同方式确定PF-74与CA六聚体互作的KD值为176 ± 78 nM [1][2]。 |
| Cell experiments | HeLa-P4 cells were inoculated with PF74 (10 μM). After 8 h of culture, the cells were harvested and DNA isolated with a DNeasy Blood & Tissue kit (Qiagen). HIV-1 DNA in the samples was quantified by real-time PCR using primers specific which shows that PF74 inhibited HIV-1 reverse transcription in target cells. |
| Target activity | HIV-1:0.72 μM(NL4.3 strain) |
| Synonyms | PF-74 |
| molecular weight | 425.52 |
| Molecular formula | C27H27N3O2 |
| CAS | 1352879-65-2 |
| Storage | |Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 249 mg/mL (585.16 mM), Sonication is recommended. |
| References | 1. Xu JP, et al. Exploring Modifications of an HIV-1 Capsid Inhibitor: Design, Synthesis, and Mechanism of Action.J Drug Des Res. 2018;5(2). pii: 1070. Epub 2018 Aug 13. 2. Shi J, et al. Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization.J Virol. 2011 Jan;85(1):542-9. |