Glecaprevir | ABT-493 | A-1282576 | CAS#1365970-03-1 | NS 3/4A inhibitor

MedKoo Cat#: 528902 | Name: Glecaprevir

Description:

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

Glecaprevir (ABT-493, A-1282576) is a potent, pangenotypic inhibitor of the hepatitis C virus (HCV) NS3/4A protease, a key enzyme essential for viral replication. It exhibits strong antiviral activity across HCV genotypes 1 through 6. In vitro, glecaprevir demonstrates EC<sub>50</sub> values ranging from 0.005 to 0.036 nM against HCV replicons of genotypes 1a, 1b, 2a, 3a, 4a, 5a, and 6a. It has high barrier to resistance and retains activity against common NS3 variants. In combination with pibrentasvir (an NS5A inhibitor), glecaprevir has shown >95% sustained virologic response (SVR12) rates in clinical trials across diverse patient populations, including those with prior treatment failure, compensated cirrhosis, or renal impairment.

Chemical Structure

Glecaprevir

CAS#1365970-03-1 (free)

Theoretical Analysis

MedKoo Cat#: 528902

Name: Glecaprevir

CAS#: 1365970-03-1 (free)

Chemical Formula: C38H46F4N6O9S

Exact Mass: 838.2983

Molecular Weight: 838.87

Elemental Analysis: C, 54.41; H, 5.53; F, 9.06; N, 10.02; O, 17.16; S, 3.82

Price and Availability

Size	Price	Availability
0.1mg	USD 1.00	Ready to Ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
10mg	USD 450.00	Ready to ship
200mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,850.00	Ready to ship
2g	USD 6,450.00	Ready to ship

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Related CAS #

1365970-03-1 (free) 1838572-01-2 (hydrate)

Synonym

ABT-493; ABT493; ABT 493; A-1282576; A 1282576; A1282576; A-1282576.0; Glecaprevir; MAVYRET.

IUPAC/Chemical Name

(3aR,7S,10S,12R,21E,24aR)-7-tert-butyl-N-{(1R,2R)-2(difluoromethyl)-1-[(1-methylcyclopropane-1-sulfonyl)carbamoyl]cyclopropyl}-20,20-difluoro5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1H,10H-9,12methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10carboxamide

InChi Key

MLSQGNCUYAMAHD-ITNVBOSISA-N

InChi Code

InChI=1S/C38H46F4N6O9S/c1-35(2,3)28-32(50)48-19-20(17-24(48)30(49)46-37(18-21(37)29(39)40)33(51)47-58(53,54)36(4)14-15-36)56-31-27(43-22-9-5-6-10-23(22)44-31)38(41,42)13-8-16-55-25-11-7-12-26(25)57-34(52)45-28/h5-6,8-10,13,20-21,24-26,28-29H,7,11-12,14-19H2,1-4H3,(H,45,52)(H,46,49)(H,47,51)/b13-8+/t20-,21+,24+,25-,26-,28-,37-/m1/s1

SMILES Code

O=C([C@H]1N(C2)C([C@H](C(C)(C)C)NC(O[C@@](CCC3)([H])[C@]3([H])OC/C=C/C(F)(F)C4=NC5=CC=CC=C5N=C4O[C@]2([H])C1)=O)=O)N[C@@]6(C(NS(=O)(C7(C)CC7)=O)=O)[C@H](C(F)F)C6

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

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

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#A9T04K26

View CoA: current batch, Lot#A9T06K03

QC Data

View QC data: current batch, Lot#A9T04K26

View QC data: current batch, Lot#A9T06K03

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Glecaprevir is a novel HCV NS3/4A protease inhibitor, with IC50 values ranging from 3.5 to 11.3 nM.

In vitro activity:

In enzymatic assays, glecaprevir exhibited a high level of selectivity for HCV NS3/4A protease over human proteases. Glecaprevir exhibits an improved resistance profile in comparison with the other PIs currently approved for the treatment of HCV infections. Glecaprevir generally demonstrated a high genetic barrier to the development of resistance in drug-resistant colony selection assays with replicon cells containing proteases from different HCV genotypes. In addition, glecaprevir displayed synergistic antiviral activity when it was combined with the NS5A inhibitor pibrentasvir. Reference: Antimicrob Agents Chemother. 2018 Jan; 62(1): e01620-17. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740381/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	69.4	82.77
	DMSO:PBS (pH 7.2) (1:1)	0.5	0.60
	DMF	25.0	29.80
	Ethanol	60.0	71.52

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 838.87 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. Timm J, Kosovrasti K, Henes M, Leidner F, Hou S, Ali A, Kurt Yilmaz N, Schiffer CA. Molecular and Structural Mechanism of Pan-Genotypic HCV NS3/4A Protease Inhibition by Glecaprevir. ACS Chem Biol. 2020 Feb 21;15(2):342-352. doi: 10.1021/acschembio.9b00675. Epub 2020 Jan 8. PMID: 31868341; PMCID: PMC7747061. 2. Ng TI, Tripathi R, Reisch T, Lu L, Middleton T, Hopkins TA, Pithawalla R, Irvin M, Dekhtyar T, Krishnan P, Schnell G, Beyer J, McDaniel KF, Ma J, Wang G, Jiang LJ, Or YS, Kempf D, Pilot-Matias T, Collins C. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS3/4A Protease Inhibitor Glecaprevir. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01620-17. doi: 10.1128/AAC.01620-17. PMID: 29084747; PMCID: PMC5740381.

In vitro protocol:

In vivo protocol:

TBD

1: Lawitz E, Flisiak R, Abunimeh M, Sise ME, Park JY, Kaskas M, Bruchfeld A, Wörns MA, Aglitti A, Zamor PJ, Xue Z, Schnell G, Jalundhwala YJ, Porcalla A, Mensa FJ, Persico M. Efficacy and Safety of Glecaprevir/Pibrentasvir in Renally-Impaired Patients with Chronic HCV Infection. Liver Int. 2019 Dec 10. doi: 10.1111/liv.14320. [Epub ahead of print] PubMed PMID: 31821716. 2: Ramirez S, Fernandez-Antunez C, Mikkelsen LS, Pedersen J, Li YP, Bukh J. Cell culture studies of the efficacy and barrier to resistance of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir against hepatitis C virus genotypes 2a, 2b and 2c. Antimicrob Agents Chemother. 2019 Dec 9. pii: AAC.01888-19. doi: 10.1128/AAC.01888-19. [Epub ahead of print] PubMed PMID: 31818814. 3: Kawaguchi I, Chayama K, Gonzalez YS, Virabhak S, Mitchell D, Yuen C, Kumada H. A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan. Adv Ther. 2019 Dec 5. doi: 10.1007/s12325-019-01166-3. [Epub ahead of print] PubMed PMID: 31808054. 4: Liu CH, Liu CJ, Hung CC, Hsieh SM, Su TH, Sun HY, Tseng TC, Chen PJ, Chen DS, Kao JH. Glecaprevir/pibrentasvir for patients with chronic hepatitis C virus infection: Real-world effectiveness and safety in Taiwan. Liver Int. 2019 Nov 11. doi: 10.1111/liv.14295. [Epub ahead of print] PubMed PMID: 31710759. 5: Brown RS Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, Horváth G, Zuckerman E, Carrion BR, Rodriguez-Perez F, Urbánek P, Abergel A, Cohen E, Lovell SS, Schnell G, Lin CW, Zha J, Wang S, Trinh R, Mensa FJ, Burroughs M, Felizarta F. Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial. J Hepatol. 2019 Nov 2. pii: S0168-8278(19)30647-6. doi: 10.1016/j.jhep.2019.10.020. [Epub ahead of print] PubMed PMID: 31682879. 6: Dore GJ, Feld JJ, Thompson A, Martinello M, Muir AJ, Agarwal K, Müllhaupt B, Wedemeyer H, Lacombe K, Matthews GV, Schultz M, Klein M, Hezode C, Estivill Mercade G, Kho D, Petoumenos K, Marks P, Tatsch F, Gabriela Pires Dos Santos A, Gane E; SMART-C Study Group. Simplified monitoring for hepatitis C virus treatment with glecaprevir plus pibrentasvir, a randomised non-inferiority trial. J Hepatol. 2019 Oct 23. pii: S0168-8278(19)30612-9. doi: 10.1016/j.jhep.2019.10.010. [Epub ahead of print] PubMed PMID: 31655134. 7: Martinello M, Orkin C, Cooke G, Bhagani S, Gane E, Kulasegaram R, Shaw D, Tu E, Petoumenos K, Marks P, Grebely J, Dore GJ, Nelson M, Matthews GV. Short duration pan-genotypic therapy with glecaprevir-pibrentasvir for six weeks among people with recent HCV infection. Hepatology. 2019 Oct 24. doi: 10.1002/hep.31003. [Epub ahead of print] PubMed PMID: 31652357. 8: Fontana RJ, Lens S, McPherson S, Elkhashab M, Ankoma-Sey V, Bondin M, Dos Santos AGP, Xue Z, Trinh R, Porcalla A, Zeuzem S. Efficacy and Safety of 8 Weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve, HCV-Infected Patients with APRI ≤ 1 in a Single-Arm, Open-Label, Multicenter Study. Adv Ther. 2019 Dec;36(12):3458-3470. doi: 10.1007/s12325-019-01123-0. Epub 2019 Oct 23. PubMed PMID: 31646465; PubMed Central PMCID: PMC6860464. 9: Toyoda H, Atsukawa M, Watanabe T, Nakamuta M, Uojima H, Nozaki A, Takaguchi K, Fujioka S, Iio E, Shima T, Akahane T, Fukunishi S, Asano T, Michitaka K, Tsuji K, Abe H, Mikami S, Okubo H, Okubo T, Shimada N, Ishikawa T, Moriya A, Tani J, Morishita A, Ogawa C, Tachi Y, Ikeda H, Yamashita N, Yasuda S, Chuma M, Tsutsui A, Hiraoka A, Ikegami T, Genda T, Tsubota A, Masaki T, Tanaka Y, Iwakiri K, Kumada T. Real-world experience of 12-week direct-acting antiviral regimen of glecaprevir and pibrentasvir in patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol. 2019 Oct 14. doi: 10.1111/jgh.14874. [Epub ahead of print] PubMed PMID: 31609495. 10: Bourliere M. Retreatment Options for Patients Who Failed Direct-Acting Antiviral Regimens Containing NS5A Inhibitors: Is Glecaprevir/Pibrentasvir a Valid and Robust Option? Gastroenterology. 2019 Dec;157(6):1473-1475. doi: 10.1053/j.gastro.2019.10.002. Epub 2019 Oct 10. PubMed PMID: 31606469. 11: Rojo E, Chaparro M, García-Buey L. Efficacy and Safety of Glecaprevir/pibrentasvir in a Patient With HCV-Induced Porphyria Cutanea Tarda Receiving Vedolizumab for Crohn´s Disease. J Crohns Colitis. 2019 Sep 17. pii: jjz159. doi: 10.1093/ecco-jcc/jjz159. [Epub ahead of print] PubMed PMID: 31602458. 12: Yoon JH, Kim SM, Kang G, Kim HJ, Jun CH, Choi SK. A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis. Medicine (Baltimore). 2019 Sep;98(39):e17343. doi: 10.1097/MD.0000000000017343. PubMed PMID: 31574875; PubMed Central PMCID: PMC6775421. 13: Brown A, Welzel TM, Conway B, Negro F, Bräu N, Grebely J, Puoti M, Aghemo A, Kleine H, Pugatch D, Mensa FJ, Chen YJ, Lei Y, Lawitz E, Asselah T. Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials. Liver Int. 2019 Sep 30. doi: 10.1111/liv.14266. [Epub ahead of print] PubMed PMID: 31568620. 14: Kaku H, Nagase K, Inoue T, Narisawa Y. An adverse skin reaction with probable nonallergic pathogenesis related to glecaprevir/pibrentasvir. Int J Dermatol. 2019 Sep 25. doi: 10.1111/ijd.14663. [Epub ahead of print] PubMed PMID: 31553053. 15: Huff J, Andersen R. Glecaprevir/Pibrentasvir: The First 8-Week, Pangenotypic HCV Treatment Regimen for Patients 12 Years of Age and Older. Ann Pharmacother. 2019 Sep 19:1060028019877128. doi: 10.1177/1060028019877128. [Epub ahead of print] PubMed PMID: 31537106. 16: Cotter TG, Jensen DM. Glecaprevir/pibrentasvir for the treatment of chronic hepatitis C: design, development, and place in therapy. Drug Des Devel Ther. 2019 Jul 29;13:2565-2577. doi: 10.2147/DDDT.S172512. eCollection 2019. PubMed PMID: 31534310; PubMed Central PMCID: PMC6681154. 17: Suleiman AA, Lin CW, Liu W, Eckert D, Mensing S, Burroughs M, Kato K, Chayama K, Kumada H, Oberoi RK. Population Pharmacokinetics of Glecaprevir/Pibrentasvir in HCV-infected Japanese Subjects in Phase 3 CERTAIN-1 and CERTAIN-2 Trials. J Clin Pharmacol. 2019 Sep 12. doi: 10.1002/jcph.1524. [Epub ahead of print] PubMed PMID: 31515816. 18: Kosloski MP, Oberoi R, Wang S, Viani RM, Asatryan A, Hu B, Ding B, Qi X, Kim EJ, Mensa F, Kort J, Liu W. Drug-Drug Interactions of Glecaprevir and Pibrentasvir Coadministered with Human Immunodeficiency Virus Antiretrovirals. J Infect Dis. 2019 Aug 29. pii: jiz439. doi: 10.1093/infdis/jiz439. [Epub ahead of print] PubMed PMID: 31504702. 19: Merli M, Rossotti R, Travi G, Ferla F, Lauterio A, Angelini Zucchetti T, Alcantarini C, Bargiacchi O, De Carlis L, Puoti M. Sustained virological response with 16-week glecaprevir/pibrentasvir after failure to sofosbuvir/velpatasvir in post-transplant severe HCV recurrence in HIV. Transpl Infect Dis. 2019 Sep 5:e13165. doi: 10.1111/tid.13165. [Epub ahead of print] PubMed PMID: 31487082. 20: Ohya K, Imamura M, Osawa M, Teraoka Y, Morio K, Fujino H, Ono A, Nakahara T, Murakami E, Yamauchi M, Kawaoka T, Hiramatsu A, Tsuge M, Aikata H, Hayes CN, Chayama K. Successful retreatment with 12 weeks of glecaprevir and pibrentasvir for a genotype 2a HCV-infected hemodialysis patient who failed to respond to 8 weeks of prior glecaprevir and pibrentasvir therapy. Clin J Gastroenterol. 2019 Aug 28. doi: 10.1007/s12328-019-01039-w. [Epub ahead of print] PubMed PMID: 31463795.