WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555985
CAS#: 2628280-40-8
Description: Nirmatrelvir, also known as PF-07321332 (brand name: Paxlovid), is an orally bioavailable 3C-like protease (3CLPRO) inhibitor and SARS-CoV-2 Mpro inhibitor. This drug is being investigated for safety, tolerability, and pharmacokinetics before moving on to studies of efficacy in the treatment or prophylaxis of COVID-19. 3CLPRO is responsible for cleaving polyproteins 1a and 1ab of SARS-CoV-2. PF-07321332 is an oral COVID-19 antiviral clinical candidate. By inhibiting the main protease, PF-07321332 prevents the virus from cleaving long protein chains into the parts it needs to reproduce itself.
MedKoo Cat#: 555985
Name: PF-07321332
CAS#: 2628280-40-8
Chemical Formula: C23H32F3N5O4
Exact Mass: 499.2406
Molecular Weight: 499.5352
Elemental Analysis: C, 55.30; H, 6.46; F, 11.41; N, 14.02; O, 12.81
Related CAS #: 2628280-40-8
Synonym: Nirmatrelvir; PF-07321332; PF 07321332; PF07321332; brand name Paxlovid;
IUPAC/Chemical Name: (1R,2S,5S)-N-((S)-1-cyano-2-((S)-2-oxopyrrolidin-3-yl)ethyl)-3-((S)-3,3-dimethyl-2-(2,2,2-trifluoroacetamido)butanoyl)-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide
InChi Key: LIENCHBZNNMNKG-OJFNHCPVSA-N
InChi Code: InChI=1S/C23H32F3N5O4/c1-21(2,3)16(30-20(35)23(24,25)26)19(34)31-10-13-14(22(13,4)5)15(31)18(33)29-12(9-27)8-11-6-7-28-17(11)32/h11-16H,6-8,10H2,1-5H3,(H,28,32)(H,29,33)(H,30,35)/t11-,12-,13-,14-,15-,16+/m0/s1
SMILES Code: [H][C@]12CN([C@H](C(=O)N[C@@H](C[C@]3([H])CCNC3=O)C#N)[C@@]1([H])C2(C)C)C(=O)[C@@H](NC(=O)C(F)(F)F)C(C)(C)C
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: To be determined
Shelf Life: >2 years if stored properly
Drug Formulation: To be determined
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | PF-07321332 targets the SARS-CoV-2 virus and can be used for COVID-19 reseacrch. IC50: 3CLPRO |
| In vitro activity: | The in vitro antiviral activity of PF-332 against the four main SARS-CoV-2 VoC was first assessed in Vero E6 and A549 (overexpressing ACE2/TMPRSS2) cells, the EC50 values obtained were between 70 and 280 nM. The antiviral effect of PF-332 was next assessed in primary human airway epithelial cell (HAEC) [that had been fully differentiated into an air-liquid (ALI) culture system] that were infected with the alpha variant (B.1.1.7). When added to the culture medium at the basolateral site of the ALI’s 1 h before infection (at the topical site) PF-332 (at 1 µM) completely inhibited viral replication for the entire duration of the experiment. At a concentration of 0.1 µM the inhibition was transient. Reference: Nat Commun. 2022 Feb 15;13(1):719. https://pubmed.ncbi.nlm.nih.gov/35169114/ |
| In vivo activity: | Female hamsters (6–8 weeks) were intranasally infected with the SARS-CoV2 beta variant (lineage B.1.351) and were orally treated with PF-332 [either at 125 or 250 mg/kg/dose, twice daily (BID)] or the vehicle (i.e., the control group) for four consecutive days whereby treatment was initiated immediately before infection. Treatment resulted in a dose-dependent reduction of viral RNA copies in lung tissue; i.e., 1.1 log10 (P = 0.0007) and 5.8 log10 (P < 0.0001) reduction in, respectively, the 125 and 250 mg/kg, BID treatment groups. Likewise the 125 mg/kg BID dose resulted in a 0.7 log10 (P = 0.03) reduction in lung infectious virus titers and treatment with 250 mg/kg BID resulted in undetectable infectious virus levels in the lungs in all the treated animals (4.4 log10 reduction, P < 0.0001). No clinical signs of adverse effects were observed in any of the PF-332-treated groups. Treatment also markedly improved virus-induced lung pathology, in particular in the 250 mg/kg BID dose whereby the lung pathology score was (in 11 out of 12 animals) comparable to the baseline score of untreated, non-infected hamsters (P < 0.0001). Reference: Nat Commun. 2022 Feb 15;13(1):719. https://pubmed.ncbi.nlm.nih.gov/35169114/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 120.0 | 240.22 |
The following data is based on the product molecular weight 499.5352 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Pavan M, Bolcato G, Bassani D, Sturlese M, Moro S. Supervised Molecular Dynamics (SuMD) Insights into the mechanism of action of SARS-CoV-2 main protease inhibitor PF-07321332. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1646-1650. doi: 10.1080/14756366.2021.1954919. PMID: 34289752. 2. Abdelnabi R, Foo CS, Jochmans D, Vangeel L, De Jonghe S, Augustijns P, Mols R, Weynand B, Wattanakul T, Hoglund RM, Tarning J, Mowbray CE, Sjö P, Escudié F, Scandale I, Chatelain E, Neyts J. The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. Nat Commun. 2022 Feb 15;13(1):719. doi: 10.1038/s41467-022-28354-0. PMID: 35169114; PMCID: PMC8847371. 3. Schooley RT, Carlin AF, Beadle JR, Valiaeva N, Zhang XQ, Clark AE, McMillan RE, Leibel SL, McVicar RN, Xie J, Garretson AF, Smith VI, Murphy J, Hostetler KY. Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs. Antimicrob Agents Chemother. 2021 Jul 26:AAC0115521. doi: 10.1128/AAC.01155-21. Epub ahead of print. PMID: 34310217. |
| In vitro protocol: | 1. Pavan M, Bolcato G, Bassani D, Sturlese M, Moro S. Supervised Molecular Dynamics (SuMD) Insights into the mechanism of action of SARS-CoV-2 main protease inhibitor PF-07321332. J Enzyme Inhib Med Chem. 2021 Dec;36(1):1646-1650. doi: 10.1080/14756366.2021.1954919. PMID: 34289752. 2. Abdelnabi R, Foo CS, Jochmans D, Vangeel L, De Jonghe S, Augustijns P, Mols R, Weynand B, Wattanakul T, Hoglund RM, Tarning J, Mowbray CE, Sjö P, Escudié F, Scandale I, Chatelain E, Neyts J. The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. Nat Commun. 2022 Feb 15;13(1):719. doi: 10.1038/s41467-022-28354-0. PMID: 35169114; PMCID: PMC8847371. |
| In vivo protocol: | 1. Schooley RT, Carlin AF, Beadle JR, Valiaeva N, Zhang XQ, Clark AE, McMillan RE, Leibel SL, McVicar RN, Xie J, Garretson AF, Smith VI, Murphy J, Hostetler KY. Rethinking Remdesivir: Synthesis, Antiviral Activity and Pharmacokinetics of Oral Lipid Prodrugs. Antimicrob Agents Chemother. 2021 Jul 26:AAC0115521. doi: 10.1128/AAC.01155-21. Epub ahead of print. PMID: 34310217. 2. Abdelnabi R, Foo CS, Jochmans D, Vangeel L, De Jonghe S, Augustijns P, Mols R, Weynand B, Wattanakul T, Hoglund RM, Tarning J, Mowbray CE, Sjö P, Escudié F, Scandale I, Chatelain E, Neyts J. The oral protease inhibitor (PF-07321332) protects Syrian hamsters against infection with SARS-CoV-2 variants of concern. Nat Commun. 2022 Feb 15;13(1):719. doi: 10.1038/s41467-022-28354-0. PMID: 35169114; PMCID: PMC8847371. |
https://cen.acs.org/acs-news/acs-meeting-news/Pfizer-unveils-oral-SARS-CoV/99/i13
