Ensitrelvir fumarate | CAS#2757470-18-9 | antiviral

MedKoo Cat#: 333079 | Name: Ensitrelvir fumarate

Description:

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

Ensitrelvir, also known as S-217622, is an antiviral drug developed by Shionogi in partnership with Hokkaido University, which acts as an orally active 3C-like protease inhibitor for the treatment of COVID-19 infection. It is taken by mouth, and has been successfully tested against the recently emerged Omicron variant. It is the first orally active non-covalent, non-peptidic, SARS-CoV-2 3CL protease inhibitor (IC50=13 nM). It became the first Japanese domestic pill to treat COVID-19, third to be regulatorally approved in Japan; in February 2022.

Chemical Structure

Ensitrelvir fumarate

CAS#2757470-18-9 (fumarate)

Theoretical Analysis

MedKoo Cat#: 333079

Name: Ensitrelvir fumarate

CAS#: 2757470-18-9 (fumarate)

Chemical Formula: C26H21ClF3N9O6

Exact Mass: 0.0000

Molecular Weight: 647.96

Elemental Analysis: C, 48.20; H, 3.27; Cl, 5.47; F, 8.80; N, 19.46; O, 14.81

Price and Availability

Size	Price	Availability
25mg	USD 125.00	Ready to ship
50mg	USD 210.00	Ready to ship
100mg	USD 350.00	Ready to ship
200mg	USD 550.00	Ready to ship
500mg	USD 1,150.00	Ready to ship
1g	USD 2,050.00	Ready to ship
2g	USD 3,650.00	Ready to ship

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

2647530-73-0 (free base) 2757470-18-9 (fumarate)

Synonym

Ensitrelvir fumarate; S-217622; S 217622; S217622; Xocova;

IUPAC/Chemical Name

(E)-6-((6-chloro-2-methyl-2H-indazol-5-yl)imino)-3-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)-1-(2,4,5-trifluorobenzyl)-1,3,5-triazinane-2,4-dione fumaric acid

InChi Key

FBOCUALVLIWPNQ-WLHGVMLRSA-N

InChi Code

InChI=1S/C22H17ClF3N9O2.C4H4O4/c1-32-7-12-4-18(13(23)5-17(12)30-32)28-20-29-21(36)35(9-19-27-10-33(2)31-19)22(37)34(20)8-11-3-15(25)16(26)6-14(11)24;5-3(6)1-2-4(7)8/h3-7,10H,8-9H2,1-2H3,(H,28,29,36);1-2H,(H,5,6)(H,7,8)/b;2-1+

SMILES Code

O=C(N(CC1=NN(C)C=N1)C(N/2)=O)N(CC3=CC(F)=C(F)C=C3F)C2=N\C4=CC5=CN(C)N=C5C=C4Cl.O=C(O)/C=C/C(O)=O

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# M22S05O13

QC Data

View QC data: current batch, Lot# M22S05O13

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Ensitrelvir (S-217622) fumarate is an active non-covalent, non-peptidic, SARS-CoV-2 3CL protease inhibitor (IC50=13 nM).

In vitro activity:

The antiviral activities were evaluated as per their inhibitory ability of the cytopathic effects elicited in SARS-CoV-2-infected VeroE6/TMPRSS2 cells. S-217622 exhibited similar antiviral activities against all tested SARS-CoV-2 variants, including the Omicron strain, which is responsible for the current wave of the pandemic, indicating its potential broad usability as a therapeutic agent for treating COVID-19 (half-maximal effective concentration [EC50] = 0.29–0.50 μM. Antiviral activity of S-217622 against SARS-CoV (EC50 = 0.21 μM). was also comparable to that against SARS-CoV-2, where the sequence homology of 3CLpro between SARS-CoV-2 and SARS-CoV was well-conserved. S-217622 also exhibited potent antiviral activity against MERS-CoV (EC50 = 1.4 μM), HCoV-OC43 (EC90 = 0.074 μM), and HCoV-229E (EC50 = 5.5 μM). S-217622 showed no inhibitory activity against host-cell proteases, such as caspase-2, chymotrypsin, cathepsin B/D/G/L, and thrombin at up to 100 μM, suggesting its high selectivity for coronavirus proteases. S-217622 exhibited no safety concerns in vitro in studies involving ether-a-go-go-related gene inhibition, mutagenicity/clastogenicity, and phototoxicity. Reference: J Med Chem. 2022 May 12;65(9):6499-6512. https://pubmed.ncbi.nlm.nih.gov/35352927/

In vivo activity:

The antiviral efficacy of S-217622 was evaluated in vivo in mice infected with SARS-CoV-2 Gamma strain. Five-week-old BALB/c mice were intranasally inoculated with SARS-CoV-2 Gamma strain (hCoV-19/Japan/TY7-501/2021), and S-217622 was administered orally as a 0.5% methylcellulose suspension immediately and 12 hours after infection. S-217622 treatment reduced the intrapulmonary viral titers dose-dependently. The mean viral titer was significantly lower in the S-217622 treatment groups than in the vehicle treatment group (2 mg/kg vs vehicle, p = 0.0289; 8, 16, and 32 mg/kg vs vehicle, p < 0.0001). Viral titers reached near the lower limit of quantification (1.80 – log10 50% tissue culture infectious dose [TCID50]/mL) at 16 and 32 mg/kg in the S-217622 treatment group. Although twice-daily treatment was applied in this mouse model, a once-daily treatment model could be applicable in clinical treatment because S-217622 showed a much lower clearance and longer elimination half-lives in nonrodents than in rodents. Reference: J Med Chem. 2022 May 12;65(9):6499-6512. https://pubmed.ncbi.nlm.nih.gov/35352927/

	Solvent	mg/mL	mM
Solubility
	DMSO	0.0	0.00

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 647.96 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. Unoh Y, Uehara S, Nakahara K, Nobori H, Yamatsu Y, Yamamoto S, Maruyama Y, Taoda Y, Kasamatsu K, Suto T, Kouki K, Nakahashi A, Kawashima S, Sanaki T, Toba S, Uemura K, Mizutare T, Ando S, Sasaki M, Orba Y, Sawa H, Sato A, Sato T, Kato T, Tachibana Y. Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19. J Med Chem. 2022 May 12;65(9):6499-6512. doi: 10.1021/acs.jmedchem.2c00117. Epub 2022 Mar 30. PMID: 35352927; PMCID: PMC8982737. 2. McKimm-Breschkin JL, Hay AJ, Cao B, Cox RJ, Dunning J, Moen AC, Olson D, Pizzorno A, Hayden FG. COVID-19, Influenza and RSV: Surveillance-informed prevention and treatment - Meeting report from an isirv-WHO virtual conference. Antiviral Res. 2022 Jan;197:105227. doi: 10.1016/j.antiviral.2021.105227. Epub 2021 Dec 18. PMID: 34933044; PMCID: PMC8684224. 3.

In vitro protocol:

In vivo protocol:

1. Kawaoka Y, Uraki R, Kiso M, Iida S, Imai M, Takashita E, Kuroda M, Halfmann P, Loeber S, Maemura T, Yamayoshi S, Fujisaki S, Wang Z, Ito M, Ujie M, Iwatsuki-Horimoto K, Furusawa Y, Wright R, Chong Z, Ozono S, Yasuhara A, Ueki H, Sakai Y, Li R, Liu Y, Larson D, Koga M, Tsutsumi T, Adachi E, Saito M, Yamamoto S, Matsubara S, Hagihara M, Mitamura K, Sato T, Hojo M, Hattori SI, Maeda K, Okuda M, Murakami J, Duong C, Godbole S, Douek D, Watanabe S, Ohmagari N, Yotsuyanagi H, Diamond M, Hasegawa H, Mitsuya H, Suzuki T. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/BA.2. Res Sq [Preprint].2022 Feb 24:rs.3.rs-1375091. doi: 10.21203/rs.3.rs-1375091/v1. PMID: 35233565; PMCID: PMC8887076. 2. 2. Unoh Y, Uehara S, Nakahara K, Nobori H, Yamatsu Y, Yamamoto S, Maruyama Y, Taoda Y, Kasamatsu K, Suto T, Kouki K, Nakahashi A, Kawashima S, Sanaki T, Toba S, Uemura K, Mizutare T, Ando S, Sasaki M, Orba Y, Sawa H, Sato A, Sato T, Kato T, Tachibana Y. Discovery of S-217622, a Noncovalent Oral SARS-CoV-2 3CL Protease Inhibitor Clinical Candidate for Treating COVID-19. J Med Chem. 2022 May 12;65(9):6499-6512. doi: 10.1021/acs.jmedchem.2c00117. Epub 2022 Mar 30. PMID: 35352927; PMCID: PMC8982737.

1: Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, Fukuhara T, Ichihashi G, Sanaki T, Baba K, Takeda Y, Tsuge Y, Uehara T. A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part. Antimicrob Agents Chemother. 2022 Oct 18;66(10):e0069722. doi: 10.1128/aac.00697-22. Epub 2022 Sep 13. PMID: 36098519; PMCID: PMC9578433. 2: McCarthy MW. Ensitrelvir as a potential treatment for COVID-19. Expert Opin Pharmacother. 2022 Dec;23(18):1995-1998. doi: 10.1080/14656566.2022.2146493. Epub 2022 Nov 10. PMID: 36350029. 3: Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y, Sakaguchi H, Sonoyama T, Ichihashi G, Sanaki T, Baba K, Tsuge Y, Uehara T. Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study. Clin Infect Dis. 2023 Apr 17;76(8):1403-1411. doi: 10.1093/cid/ciac933. PMID: 36477182; PMCID: PMC10110269. 4: Nobori H, Fukao K, Kuroda T, Anan N, Tashima R, Nakashima M, Noda S, Tajiri M, Torii M, Toba S, Uemura K, Sanaki T, Shishido T, Tachibana Y, Kato T. Efficacy of ensitrelvir against SARS-CoV-2 in a delayed-treatment mouse model. J Antimicrob Chemother. 2022 Oct 28;77(11):2984-2991. doi: 10.1093/jac/dkac257. PMID: 35914182; PMCID: PMC9384569. 5: Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. Safety, Tolerability, and Pharmacokinetics of the Novel Antiviral Agent Ensitrelvir Fumaric Acid, a SARS-CoV-2 3CL Protease Inhibitor, in Healthy Adults. Antimicrob Agents Chemother. 2022 Oct 18;66(10):e0063222. doi: 10.1128/aac.00632-22. Epub 2022 Sep 12. PMID: 36094202; PMCID: PMC9578392. 6: Heilmann E, Costacurta F, Moghadasi SA, Ye C, Pavan M, Bassani D, Volland A, Ascher C, Weiss AKH, Bante D, Harris RS, Moro S, Rupp B, Martinez-Sobrido L, von Laer D. SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376. Sci Transl Med. 2023 Jan 11;15(678):eabq7360. doi: 10.1126/scitranslmed.abq7360. Epub 2023 Jan 11. PMID: 36194133; PMCID: PMC9765458. 7: Kuroda T, Nobori H, Fukao K, Baba K, Matsumoto K, Yoshida S, Tanaka Y, Watari R, Oka R, Kasai Y, Inoue K, Kawashima S, Shimba A, Hayasaki-Kajiwara Y, Tanimura M, Zhang Q, Tachibana Y, Kato T, Shishido T. Efficacy comparison of 3CL protease inhibitors ensitrelvir and nirmatrelvir against SARS-CoV-2 in vitro and in vivo. J Antimicrob Chemother. 2023 Apr 3;78(4):946-952. doi: 10.1093/jac/dkad027. PMID: 36760083; PMCID: PMC10068418. 8: Kawashima S, Matsui Y, Adachi T, Morikawa Y, Inoue K, Takebayashi S, Nobori H, Rokushima M, Tachibana Y, Kato T. Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally. Biochem Biophys Res Commun. 2023 Feb 19;645:132-136. doi: 10.1016/j.bbrc.2023.01.040. Epub 2023 Jan 14. PMID: 36689809; PMCID: PMC9839456. 9: Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T, Sonoyama T, Ichihashi G, Sanaki T, Tsuge Y, Uehara T, Mukae H. A phase 2/3 study of S-217622 in participants with SARS-CoV-2 infection (Phase 3 part). Medicine (Baltimore). 2023 Feb 22;102(8):e33024. doi: 10.1097/MD.0000000000033024. PMID: 36827007; PMCID: PMC9949372. 10: Uraki R, Kiso M, Iida S, Imai M, Takashita E, Kuroda M, Halfmann PJ, Loeber S, Maemura T, Yamayoshi S, Fujisaki S, Wang Z, Ito M, Ujie M, Iwatsuki-Horimoto K, Furusawa Y, Wright R, Chong Z, Ozono S, Yasuhara A, Ueki H, Sakai-Tagawa Y, Li R, Liu Y, Larson D, Koga M, Tsutsumi T, Adachi E, Saito M, Yamamoto S, Hagihara M, Mitamura K, Sato T, Hojo M, Hattori SI, Maeda K, Valdez R; IASO study team; Okuda M, Murakami J, Duong C, Godbole S, Douek DC, Maeda K, Watanabe S, Gordon A, Ohmagari N, Yotsuyanagi H, Diamond MS, Hasegawa H, Mitsuya H, Suzuki T, Kawaoka Y. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron BA.2. Nature. 2022 Jul;607(7917):119-127. doi: 10.1038/s41586-022-04856-1. Epub 2022 May 16. PMID: 35576972; PMCID: PMC10579982. 11: Lin M, Zeng X, Duan Y, Yang Z, Ma Y, Yang H, Yang X, Liu X. Molecular mechanism of ensitrelvir inhibiting SARS-CoV-2 main protease and its variants. Commun Biol. 2023 Jul 5;6(1):694. doi: 10.1038/s42003-023-05071-y. PMID: 37407698; PMCID: PMC10322880. 12: Sakamaki I, Negoro E, Iwasaki H, Yamauchi T. Ensitrelvir eradicates persistent SARS-CoV-2 infection in a follicular lymphoma patient treated with anti-CD20 antibodies. J Infect Chemother. 2023 Sep 9:S1341-321X(23)00212-X. doi: 10.1016/j.jiac.2023.09.008. Epub ahead of print. PMID: 37690521. 13: Kiso M, Yamayoshi S, Iida S, Furusawa Y, Hirata Y, Uraki R, Imai M, Suzuki T, Kawaoka Y. In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir. Nat Commun. 2023 Jul 15;14(1):4231. doi: 10.1038/s41467-023-40018-1. PMID: 37454219; PMCID: PMC10349878. 14: Yang Y, Cao L, Yan M, Zhou J, Yang S, Xu T, Huang S, Li K, Zhou Q, Li G, Zhu Y, Cong F, Zhang H, Guo D, Li Y, Zhang X. Synthesis of deuterated S-217622 (Ensitrelvir) with antiviral activity against coronaviruses including SARS- CoV-2. Antiviral Res. 2023 May;213:105586. doi: 10.1016/j.antiviral.2023.105586. Epub 2023 Mar 28. PMID: 36997073; PMCID: PMC10043954. 15: Noske GD, de Souza Silva E, de Godoy MO, Dolci I, Fernandes RS, Guido RVC, Sjö P, Oliva G, Godoy AS. Structural basis of nirmatrelvir and ensitrelvir activity against naturally occurring polymorphisms of the SARS-CoV-2 main protease. J Biol Chem. 2023 Mar;299(3):103004. doi: 10.1016/j.jbc.2023.103004. Epub 2023 Feb 10. PMID: 36775130; PMCID: PMC9916189. 16: Kawajiri T, Kijima A, Iimuro A, Ohashi E, Yamakawa K, Agura K, Masuda K, Kouki K, Kasamatsu K, Yanagisawa S, Nakashima S, Shibahara S, Toyota T, Higuchi T, Suto T, Oohara T, Maki T, Sahara N, Fukui N, Wakamori H, Ikemoto H, Murakami H, Ando H, Hosoya M, Sato M, Suzuki Y, Nakagawa Y, Unoh Y, Hirano Y, Nagasawa Y, Goda S, Ohara T, Tsuritani T. Development of a Manufacturing Process toward the Convergent Synthesis of the COVID-19 Antiviral Ensitrelvir. ACS Cent Sci. 2023 Apr 7;9(4):836-843. doi: 10.1021/acscentsci.2c01203. PMID: 37122445; PMCID: PMC10108738. 17: Shimizu R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. A Phase 1 Study of Ensitrelvir Fumaric Acid Tablets Evaluating the Safety, Pharmacokinetics and Food Effect in Healthy Adult Populations. Clin Drug Investig. 2023 Oct;43(10):785-797. doi: 10.1007/s40261-023-01309-z. Epub 2023 Oct 5. PMID: 37798608; PMCID: PMC10575992. 18: Ferraro S, Convertino I, Cappello E, Valdiserra G, Bonaso M, Tuccori M. Lessons learnt from the preclinical discovery and development of ensitrelvir as a COVID-19 therapeutic option. Expert Opin Drug Discov. 2023 Oct 13:1-12. doi: 10.1080/17460441.2023.2267001. Epub ahead of print. PMID: 37830361. 19: Sasaki M, Tabata K, Kishimoto M, Itakura Y, Kobayashi H, Ariizumi T, Uemura K, Toba S, Kusakabe S, Maruyama Y, Iida S, Nakajima N, Suzuki T, Yoshida S, Nobori H, Sanaki T, Kato T, Shishido T, Hall WW, Orba Y, Sato A, Sawa H. S-217622, a SARS-CoV-2 main protease inhibitor, decreases viral load and ameliorates COVID-19 severity in hamsters. Sci Transl Med. 2023 Jan 18;15(679):eabq4064. doi: 10.1126/scitranslmed.abq4064. Epub 2023 Jan 18. PMID: 36327352; PMCID: PMC9765455. 20: Shimizu R, Matsuzaki T, Oka R, Sonoyama T, Fukuhara T, Kuwata A, Matsuo Y, Kubota R. Evaluation of Drug-Drug Interactions of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor, With Transporter Substrates Based on In Vitro and Clinical Studies. J Clin Pharmacol. 2023 Aug;63(8):918-927. doi: 10.1002/jcph.2247. Epub 2023 May 10. PMID: 37043676.