Asunaprevir

• CAT Number: I004375
• CAS Number: 630420-16-5
• Molecular Formula: C35H46ClN5O9S
• Molecular Weight: 748.3
• Purity: ≥95%
• Synonyms: tert-butyl N-[(2S)-1-[(2S,4R)-4-(7-chloro-4-methoxyisoquinolin-1-yl)oxy-2-[[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]carbamate
• Target: HCV Protease
• Solubility: DMSO: ≥ 42.9 mg/mL
• Storage: Store at -20°C
• InChI: InChI=1S/C35H46ClN5O9S/c1-9-19-16-35(19,31(44)40-51(46,47)22-11-12-22)39-28(42)25-15-21(49-29-24-14-20(36)10-13-23(24)26(48-8)17-37-29)18-41(25)30(43)27(33(2,3)4)38-32(45)50-34(5,6)7/h9-10,13-14,17,19,21-22,25,27H,1,11-12,15-16,18H2,2-8H3,(H,38,45)(H,39,4
• InChIKey: XRWSZZJLZRKHHD-QGQNBIQGSA-N
• SMILES: O=C(N[C@@]1(C(NS(C2CC2)(=O)=O)=O)[C@H](C=C)C1)[C@H]3N(C([C@H](C(C)(C)C)NC(OC(C)(C)C)=O)=O)C[C@@H](OC4=C(C=C(Cl)C=C5)C5=C(OC)C=N4)C3

Asunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) NS3 protease inhibitor.IC50 Value:Target: HCV NS3/4A Protease; HCVAsunaprevir (BMS-650032) is a potent hepatitis C virus (HCV) non-structural protein protease inhibitor currently in Phase III clinical trials for the treatment of HCV infection. A rugged and accurate LC-MS/MS method was developed and validated for the quantitation of asunaprevir in rat, dog, monkey, rabbit and mouse plasma. A systematic method screening and optimization strategy was applied to achieve optimized mass spectrometry, chromatography, and sample extraction conditions. Asunaprevir-resistant replicons remained susceptible to an NS5A replication complex inhibitor, consistent with a role for asunaprevir in combination therapies.

Reference

1:Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus. Tsai WL, Cheng JS, Shu CW, Lai KH, Chan HH, Wu CC, Wu JM, Hsu PI, Chung RT, Chang TH.Front Microbiol. 2017 Apr 20;8:668. doi: 10.3389/fmicb.2017.00668. eCollection 2017. PMID: 28473813 Free PMC Article2:Efficacy and safety of dual therapy with daclatasvir and asunaprevir in elderly patients. Tarao K, Tanaka K, Nozaki A, Sato A, Ishii T, Komatsu H, Ikeda T, Komatsu T, Matsushima S, Oshige K.World J Hepatol. 2017 Apr 18;9(11):544-550. doi: 10.4254/wjh.v9.i11.544. PMID: 28469810 Free PMC Article3:Daclatasvir/Asunaprevir/Beclabuvir (DCV-TRIO), All-Oral, Fixed-Dose Combination for Patients With Chronic HCV Genotype 1. Kao JH, Yu ML, Peng CY, Heo J, Chu CJ, Chang TT, Lee YJ, Hu TH, Yoon KT, Paik SW, Lim YS, Ahn SH, Isakov V, McPhee F, Hu W, Swenson ES, Yin PD, Treitel M.J Gastroenterol Hepatol. 2017 Mar 31. doi: 10.1111/jgh.13796. [Epub ahead of print] PMID: 28370350 4:Daclatasvir/asunaprevir based direct-acting antiviral therapy ameliorate hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis: a case report. Shimada M, Nakamura N, Endo T, Yamabe H, Nakamura M, Murakami R, Narita I, Tomita H.BMC Nephrol. 2017 Mar 29;18(1):109. doi: 10.1186/s12882-017-0534-5. PMID: 28356063 Free PMC Article5:Clinical evaluation of sofosbuvir/ledipasvir in patients with chronic hepatitis C genotype 1 with and without prior daclatasvir/asunaprevir therapy. Iio E, Shimada N, Takaguchi K, Senoh T, Eguchi Y, Atsukawa M, Tsubota A, Abe H, Kato K, Kusakabe A, Miyaki T, Matsuura K, Matsunami K, Shinkai N, Fujiwara K, Nojiri S, Tanaka Y.Hepatol Res. 2017 Mar 22. doi: 10.1111/hepr.12898. [Epub ahead of print] PMID: 28332272 6:Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy. Suda G, Ogawa K, Yamamoto Y, Katagiri M, Furuya K, Kumagai K, Konno J, Kimura M, Kawagishi N, Ohara M, Umemura M, Ito J, Izumi T, Nakai M, Sho T, Natsuizaka M, Morikawa K, Tsubota A, Shimada N, Iio E, Tanaka Y, Sakamoto N; NORTE Study Group..J Gastroenterol. 2017 Mar 18. doi: 10.1007/s00535-017-1328-z. [Epub ahead of print] PMID: 28315983 7:Efficacy and safety of daclatasvir plus asunaprevir for Korean patients with HCV genotype Ib infection: a retrospective multi-institutional study. Cho BW, Kim SB, Song IH, Lee SH, Kim HS, Lee TH, Kang YW, Kim SH, Lee BS, Chae HB.Clin Mol Hepatol. 2017 Mar;23(1):51-56. doi: 10.3350/cmh.2016.0053. Epub 2017 Mar 16. PMID: 28297836 Free PMC Article8:Asunaprevir: An HCV Protease Inhibitor With Preferential Liver Distribution. Eley T, Garimella T, Li W, Bertz RJ.Clin Pharmacol Drug Dev. 2017 Mar;6(2):195-200. doi: 10.1002/cpdd.315. PMID: 28263460 9:Daclatasvir and asunaprevir treatment in patients with severe liver fibrosis by HCV genotype 1b infection: Real world data. Ishigami M, Hayashi K, Honda T, Kuzuya T, Ishizu Y, Ishikawa T, Nakano I, Urano F, Kumada T, Yoshioka K, Goto H, Hirooka Y.J Gastroenterol Hepatol. 2017 Mar 4. doi: 10.1111/jgh.13779. [Epub ahead of print] PMID: 28258705 10:Daclatasvir and asunaprevir for genotype 1b chronic hepatitis C patients with chronic kidney disease. Kondo C, Atsukawa M, Tsubota A, Shimada N, Abe H, Asano T, Yoshizawa K, Okubo T, Chuganji Y, Aizawa Y, Iio E, Tanaka Y, Iwakiri K.Hepatol Res. 2017 Feb 22. doi: 10.1111/hepr.12879. [Epub ahead of print] PMID: 28225572