Nirmatrelvir | CAS#2628280-40-8 | 3CLPRO inhibitor

MedKoo Cat#: 555985 | Name: PF-07321332

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

PF-07321332

CAS#2628280-40-8

Theoretical Analysis

MedKoo Cat#: 555985

Name: PF-07321332

CAS#: 2628280-40-8

Chemical Formula: C23H32F3N5O4

Exact Mass: 499.2406

Molecular Weight: 499.54

Elemental Analysis: C, 55.30; H, 6.46; F, 11.41; N, 14.02; O, 12.81

Price and Availability

Size	Price	Availability
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
500mg	USD 1,650.00	Ready to ship
1g	USD 2,550.00	Ready to ship
2g	USD 4,050.00	Ready to ship
5g	USD 6,450.00	Ready to ship

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# M21S12C09

View CoA: current batch, Lot#C22R06B23

QC Data

View QC data: current batch, Lot#C22R06B23

View QC data: current batch, Lot# M21S12C09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM	comments
Solubility
	DMSO	120.0	240.22

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 499.54 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:

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.

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