PF-3450074 (also known as PF74) is a HIV-1 capsid-targeting small molecule antiviral compound which directly binds to the capsid (CA) protein at a site also utilized by host cell proteins CPSF6 and NUP153. The RNA genome of human immunodeficiency virus type 1 (HIV-1) is enclosed in a cone-shaped capsid shell that disassembles following cell entry via a process known as uncoating. During HIV-1 infection, the capsid is important for reverse transcription and entry of the virus into the target cell nucleus. The small molecule PF74 inhibits HIV-1 infection at early stages by binding to the capsid and perturbing uncoating.
Physicochemical Properties
| Molecular Formula | C27H27N3O2 |
| Molecular Weight | 425.53 |
| Exact Mass | 425.21 |
| Elemental Analysis | C, 76.21; H, 6.40; N, 9.87; O, 7.52 |
| CAS # | 1352879-65-2 |
| Related CAS # | 1352879-65-2; |
| PubChem CID | 49800090 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 4.8 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 32 |
| Complexity | 626 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | N1C2=C(C=CC=C2)C(CC(N[C@@H](CC2=CC=CC=C2)C(N(C)C2=CC=CC=C2)=O)=O)=C1C |
| InChi Key | ACDFWSNAQWFRRF-VWLOTQADSA-N |
| InChi Code | InChI=1S/C27H27N3O2/c1-19-23(22-15-9-10-16-24(22)28-19)18-26(31)29-25(17-20-11-5-3-6-12-20)27(32)30(2)21-13-7-4-8-14-21/h3-16,25,28H,17-18H2,1-2H3,(H,29,31)/t25-/m0/s1 |
| Chemical Name | 2-Methyl-N-[(1S)-2-(methylphenylamino)-2-oxo-1-(phenylmethyl)ethyl]- 1H-indole-3-acetamide |
| Synonyms | PF74; PF-74; PF 74; PF-3450074; PF 3450074; PF3450074; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | NL4.3 strain（IC50=0.72 μM） |
| ln Vitro |
PF-3450074, also known as PF-74, demonstrates antiviral properties against the HIV T107N mutant and HIV wild type NL4-3, with EC50 values of 4.5μM and 0.72μM, respectively[1]. In primary human peripheral blood mononuclear cells (PBMCs), PF-3450074 (PF-74) exhibits good potency, inhibiting 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. The median IC50 and CC50 values for this compound are 0.9 ± 0.5 μM and 90.5 ± 5.9 μM, respectively[1]. Derived similarly to NUP153, the KD for the interaction between PF-74 and the CA hexamer is found to be 176 ± 78 nM[1]. PF-3450074 (PF-74) (10 μM; 8 hours) significantly lowers the late products of reverse transcription in stocks of DNase I-treated Env-defective HIV-1 (R9.Env-) in HeLa-P4 cells[2]. |
| Cell Assay |
Cell Line: HeLa-P4 cells Concentration: 10 μM Incubation Time: 8 hours Result: prevented target cells from undergoing HIV-1 reverse transcription. |
| References |
[1]. J Drug Des Res. 2018;5(2). pii: 1070. Epub 2018 Aug 13. [2]. J Virol. 2011 Jan;85(1):542-9. [3]. J Virol.2016 May 27;90(12):5808-5823. [4]. J Virol.2018 Sep 26;92(20). pii: e00845-18. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~250 mg/mL (~587.52 mM） |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (14.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly. Solubility in Formulation 2: 10% DMSO+90% Corn Oil: ≥ 6.25 mg/mL (14.69 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3500 mL | 11.7501 mL | 23.5001 mL | |
| 5 mM | 0.4700 mL | 2.3500 mL | 4.7000 mL | |
| 10 mM | 0.2350 mL | 1.1750 mL | 2.3500 mL |