WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H465984
CAS#: 2647530-73-0 (free base)
Description: 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.
Hodoodo Cat#: H465984
Name: Ensitrelvir
CAS#: 2647530-73-0 (free base)
Chemical Formula: C22H17ClF3N9O2
Exact Mass: 531.11
Molecular Weight: 531.884
Elemental Analysis: C, 49.68; H, 3.22; Cl, 6.66; F, 10.72; N, 23.70; O, 6.02
Related CAS #: 2647530-73-0 (free base) 2757470-18-9 (fumarate)
Synonym: Ensitrelvir; 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
InChi Key: QMPBBNUOBOFBFS-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H17ClF3N9O2/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/h3-7,10H,8-9H2,1-2H3,(H,28,29,36)
SMILES Code: FC1=CC(CN(C(N2CC3=NN(C)C=N3)=O)/C(NC2=O)=N/C4=CC5=CN(C)N=C5C=C4Cl)=C(F)C=C1F
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:
| Biological target: | Ensitrelvir (S-217622) 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 160.0 | 300.82 |
The following data is based on the product molecular weight 531.88 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. 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. |
| In vitro 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. |
| 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. 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: Patnin S, Makarasen A, Vijitphan P, Baicharoen A, Chaivisuthangkura A, Kuno M, Techasakul S. Computational Screening of Phenylamino-Phenoxy-Quinoline Derivatives against the Main Protease of SARS-CoV-2 Using Molecular Docking and the ONIOM Method. Molecules. 2022 Mar 9;27(6):1793. doi: 10.3390/molecules27061793. PMID: 35335157; PMCID: PMC8955101.
2: 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.
3: 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.
