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Chemistry

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Also known as: Abt-493, Glecaprevir [usan], 1365970-03-1, A-1282576.0, K6buu8j72p, A-1282576
Molecular Formula
C38H46F4N6O9S
Molecular Weight
838.9  g/mol
InChI Key
MLSQGNCUYAMAHD-ITNVBOSISA-N
FDA UNII
K6BUU8J72P

Glecaprevir
Glecaprevir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS3/4A protease inhibitor that targets the the viral RNA replication. In combination with [DB13878], glecaprevir is a useful therapy for patients who experienced therapeutic failure from other NS3/4A protease inhibitors. It demonstrates a high genetic barrier against resistance mutations of the virus. In cell cultures, the emergence of amino acid substitutions at NS3 resistance-associated positions A156 or D/Q168 in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility to glecaprevir. The combinations of amino acid substitutions at NS3 position Y65H and D/Q168 also results in greater reductions in glecaprevir susceptibility, and NS3 Q80R in genotype 3a patients also leads to glecaprevir resistance. Glecaprevir is available as an oral combination therapy with [DB13878] under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of 93% across genotypes 1a, 2a, 3a, 4, 5 and 6.
Glecaprevir is a Hepatitis C Virus NS3/4A Protease Inhibitor. The mechanism of action of glecaprevir is as a HCV NS3/4A Protease Inhibitor, and P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor, and Organic Anion Transporting Polypeptide 1B1 Inhibitor, and Organic Anion Transporting Polypeptide 1B3 Inhibitor, and Cytochrome P450 3A Inhibitor, and Cytochrome P450 1A2 Inhibitor, and UGT1A1 Inhibitor.
1 2D Structure

Glecaprevir

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(1R,14E,18R,22R,26S,29S)-26-tert-butyl-N-[(1R,2R)-2-(difluoromethyl)-1-[(1-methylcyclopropyl)sulfonylcarbamoyl]cyclopropyl]-13,13-difluoro-24,27-dioxo-2,17,23-trioxa-4,11,25,28-tetrazapentacyclo[26.2.1.03,12.05,10.018,22]hentriaconta-3,5,7,9,11,14-hexaene-29-carboxamide
2.1.2 InChI
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
2.1.3 InChI Key
MLSQGNCUYAMAHD-ITNVBOSISA-N
2.1.4 Canonical SMILES
CC1(CC1)S(=O)(=O)NC(=O)C2(CC2C(F)F)NC(=O)C3CC4CN3C(=O)C(NC(=O)OC5CCCC5OCC=CC(C6=NC7=CC=CC=C7N=C6O4)(F)F)C(C)(C)C
2.1.5 Isomeric SMILES
CC1(CC1)S(=O)(=O)NC(=O)[C@]2(C[C@H]2C(F)F)NC(=O)[C@@H]3C[C@@H]4CN3C(=O)[C@@H](NC(=O)O[C@@H]5CCC[C@H]5OC/C=C/C(C6=NC7=CC=CC=C7N=C6O4)(F)F)C(C)(C)C
2.2 Other Identifiers
2.2.1 UNII
K6BUU8J72P
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Abt-493

2.3.2 Depositor-Supplied Synonyms

1. Abt-493

2. Glecaprevir [usan]

3. 1365970-03-1

4. A-1282576.0

5. K6buu8j72p

6. A-1282576

7. A-12825760

8. 1365970-03-1 (free)

9. Abt 493

10. (3ar,7s,10s,12r,21e,24ar)-7-tert-butyl-n-[(1r,2r)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1h,10h-9,12-methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10-carboxamide

11. (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

12. Unii-k6buu8j72p

13. Maviret

14. (3ar,7s,10s,12r,21e,24ar)-7-tert-butyl-n-[(1r,2r)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclop Ropyl]-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1h,10h-9,12-methanocyclopenta[18,19][1,10,17, 3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10-carboxamide

15. O31

16. Glecaprevir [mi]

17. Abt-493(glecaprevir)

18. Glecaprevir [inn]

19. Glecaprevir (usan/inn)

20. Glecaprevir [who-dd]

21. Schembl883097

22. Abt493

23. Chembl3545363

24. Gtpl11267

25. Glecaprevir [orange Book]

26. Dtxsid901027945

27. (1r,14e,18r,22r,26s,29s)-26-tert-butyl-n-[(1r,2r)-2-(difluoromethyl)-1-[(1-methylcyclopropyl)sulfonylcarbamoyl]cyclopropyl]-13,13-difluoro-24,27-dioxo-2,17,23-trioxa-4,11,25,28-tetrazapentacyclo[26.2.1.03,12.05,10.018,22]hentriaconta-3,5,7,9,11,14-hexaene-29-carboxamide

28. Amy38157

29. Ex-a1940

30. Mavyret Component Glecaprevir

31. Bdbm50573891

32. S5720

33. Cs-8098

34. Db13879

35. Ac-33419

36. Hy-17634

37. J3.646.120i

38. D10814

39. 3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10-carboxamide

40. (3ar,7s,10s,12r,21e,24ar)-7-tert-butyl-n-((1r,2r)-2-(difluoromethyl)-1-((1-methylcyclopropane-1-sulfonyl)carbamoyl)cyclopropyl)-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1h,10h-9,12-methanocyclopenta(18,19)(1,10,17,3,6)trioxadiazacyclononadecino(11,12-b)quinoxaline-10-carboxamide

41. (3ar,7s,10s,12r,21e,24ar)-7-tert-butyl-n-[(1r,2r)-2-(difluoromethyl)-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclop

42. (3ar,7s,10s,12r,21e,24ar)-7-tert-butyl-n-{(1r,2r)-2- (difluoromethyl)-1-[(1-methylcyclopropane-1-sulfonyl)carbamoyl]cyclopropyl}-20,20-difluoro- 5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1h,10h-9,12- Methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10- Carboxamide Hydrate

43. Cyclopropanecarboxamide, N-((((1r,2r)-2-((4,4-difluoro-4-(3-hydroxy-2-quinoxalinyl)-2-buten-1-yl)oxy)cyclopentyl)oxy)carbonyl)-3-methyl-l-valyl-(4r)-4-hydroxy-l-prolyl-1-amino-2-(difluoromethyl)-n-((1-methylcyclopropyl)sulfonyl)-, Cyclic (1->2)-ether, (1r,2r)-

44. Ropyl]-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1h,10h-9,12-methanocyclopenta[18,19][1,10,17,

2.4 Create Date
2012-11-30
3 Chemical and Physical Properties
Molecular Weight 838.9 g/mol
Molecular Formula C38H46F4N6O9S
XLogP34.6
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count15
Rotatable Bond Count7
Exact Mass838.29831089 g/mol
Monoisotopic Mass838.29831089 g/mol
Topological Polar Surface Area204 Ų
Heavy Atom Count58
Formal Charge0
Complexity1760
Isotope Atom Count0
Defined Atom Stereocenter Count7
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count1
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is also indicated for the treatment of adult patients with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both.


FDA Label


Maviret is indicated for the treatment of chronic hepatitis C virus (HCV) infection in adults and children aged 3 years and older.

Maviret coated granules is indicated for the treatment of chronic hepatitis C virus (HCV) infection in children 3 years and older.


5 Pharmacology and Biochemistry
5.1 Pharmacology

In a biochemical assay studying clinical isolates of HCV genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a, and 6a, glecaprevir displayed IC50 values ranging from 3.5 to 11.3 nM that resulted in inhibition of the proteolytic activity of recombinant NS3/4A enzymes. In HCV replicon assays, glecaprevir had median EC50 values of 0.08-4.6 nM against laboratory and clinical isolates from subtypes 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, and 6a. In a QT study, glecaprevir is not shown to prolong the QTc interval.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
GLECAPREVIR
5.2.2 FDA UNII
K6BUU8J72P
5.2.3 Pharmacological Classes
Mechanisms of Action [MoA] - UGT1A1 Inhibitors
5.3 ATC Code

J05AP57


5.4 Absorption, Distribution and Excretion

Absorption

In healthy subjects, the time it takes to reach the peak plasma concentration (Tmax) is approximately 5 hours. The mean peak plasma concentration (Cmax) is 597ng/mL in non-cirrhotic HCV-infected subjects. Relative to fasting conditions, the consumption of meals increases the absorption of glecaprevir by 83-163%.


Route of Elimination

The predominant route of elimination of the drug is biliary-fecal, where 92.1% of administered drug is excreted in feces and 0.7% of the drug is excreted in the urine.


5.5 Metabolism/Metabolites

Glecaprevir undergoes limited secondary metabolism in vitro, predominantly by CYP3A.


5.6 Biological Half-Life

The elimination half life (t1/2) is approximately 6 hours.


5.7 Mechanism of Action

Glecaprevir is an inhibitor of the HCV NS3/4A protease, which is a viral enzyme necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins. These multifunctional proteins, including NS3, are essential for viral replication. The N-terminal of NS3 protein confers serine protease activity, whileThe C-terminus of NS3 encodes a DExH/D-box RNA helicase which hydyolyzes NTP as an energy source to unwind double-stranded RNA in a 3 to 5 direction during replication of viral genomic RNA. NS4A is a cofactor for NS3 that directs the localization of NS3 and modulates its enzymatic activities. Glecaprevir disrupts the intracellular processes of the viral life cycle through inhibiting the NS3/4A protease activity of cleaving downstream junctions of HCV polypeptide and proteolytic processing of mature structural proteins.


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ABOUT THIS PAGE

Looking for 1365970-03-1 / Glecaprevir API manufacturers, exporters & distributors?

Glecaprevir manufacturers, exporters & distributors 1

53

PharmaCompass offers a list of Glecaprevir API manufacturers, exporters & distributors, which can be sorted by GMP, USDMF, JDMF, KDMF, CEP (COS), WC, Price,and more, enabling you to easily find the right Glecaprevir manufacturer or Glecaprevir supplier for your needs.

Send us enquiries for free, and we will assist you in establishing a direct connection with your preferred Glecaprevir manufacturer or Glecaprevir supplier.

PharmaCompass also assists you with knowing the Glecaprevir API Price utilized in the formulation of products. Glecaprevir API Price is not always fixed or binding as the Glecaprevir Price is obtained through a variety of data sources. The Glecaprevir Price can also vary due to multiple factors, including market conditions, regulatory modifications, or negotiated pricing deals.

API | Excipient name

Glecaprevir

Synonyms

Abt-493, Glecaprevir [usan], 1365970-03-1, A-1282576.0, K6buu8j72p, A-1282576

Cas Number

1365970-03-1

Unique Ingredient Identifier (UNII)

K6BUU8J72P

About Glecaprevir

Glecaprevir is a direct acting antiviral agent and Hepatitis C virus (HCV) NS3/4A protease inhibitor that targets the the viral RNA replication. In combination with [DB13878], glecaprevir is a useful therapy for patients who experienced therapeutic failure from other NS3/4A protease inhibitors. It demonstrates a high genetic barrier against resistance mutations of the virus. In cell cultures, the emergence of amino acid substitutions at NS3 resistance-associated positions A156 or D/Q168 in HCV genotype 1a, 2a or 3a replicons led to reduced susceptibility to glecaprevir. The combinations of amino acid substitutions at NS3 position Y65H and D/Q168 also results in greater reductions in glecaprevir susceptibility, and NS3 Q80R in genotype 3a patients also leads to glecaprevir resistance. Glecaprevir is available as an oral combination therapy with [DB13878] under the brand name Mavyret. This fixed-dose combination therapy was FDA-approved in August 2017 to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also indicated for HCV genotype 1-infected patients who have been previously treated with regimens either containing an NS5A inhibitor or an NS3/4A protease inhibitor, but not both. Hepatitis C viral infection often leads to decreased liver function and subsequent liver failure, causing a significantly negative impact on the patients' quality of life. The ultimate goal of the combination treatment is to achieve sustained virologic response (SVR) and cure the patients from the infection. In clinical trials, this combination therapy achieved SVR12 rate, or undetectable Hepatitis C for twelve or more weeks after the end of treatment, of 93% across genotypes 1a, 2a, 3a, 4, 5 and 6.

Glecaprevir Manufacturers

A Glecaprevir manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Glecaprevir, including repackagers and relabelers. The FDA regulates Glecaprevir manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Glecaprevir API Manufacturers are required to adhere to Good Manufacturing Practices (GMP) to ensure that their products are consistently manufactured to meet established quality criteria.

click here to find a list of Glecaprevir manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Glecaprevir Suppliers

A Glecaprevir supplier is an individual or a company that provides Glecaprevir active pharmaceutical ingredient (API) or Glecaprevir finished formulations upon request. The Glecaprevir suppliers may include Glecaprevir API manufacturers, exporters, distributors and traders.

click here to find a list of Glecaprevir suppliers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PharmaCompass.

Glecaprevir KDMF

In Korea, the Ministry of Food and Drug Safety (MFDS) is in charge of regulating pharmaceutical products and services.

Pharmaceutical companies submit a Glecaprevir Drug Master File in Korea (Glecaprevir KDMF) to the MFDS, which includes comprehensive information about the production, processing, facilities, materials, packaging, and testing of Glecaprevir. The MFDS reviews the Glecaprevir KDMF as part of the drug registration process and uses the information provided in the Glecaprevir KDMF to evaluate the safety and efficacy of the drug.

After submitting a Glecaprevir KDMF to the MFDS, the registered manufacturer can provide importers or distributors with the registration number without revealing confidential information to Korean business partners. Applicants seeking to register their Glecaprevir API can apply through the Korea Drug Master File (KDMF).

click here to find a list of Glecaprevir suppliers with KDMF on PharmaCompass.

Glecaprevir GMP

Glecaprevir Active pharmaceutical ingredient (API) is produced in GMP-certified manufacturing facility.

GMP stands for Good Manufacturing Practices, which is a system used in the pharmaceutical industry to make sure that goods are regularly produced and monitored in accordance with quality standards. The FDA’s current Good Manufacturing Practices requirements are referred to as cGMP or current GMP which indicates that the company follows the most recent GMP specifications. The World Health Organization (WHO) has its own set of GMP guidelines, called the WHO GMP. Different countries can also set their own guidelines for GMP like China (Chinese GMP) or the EU (EU GMP).

PharmaCompass offers a list of Glecaprevir GMP manufacturers, exporters & distributors, which can be sorted by USDMF, JDMF, KDMF, CEP (COS), WC, API price, and more, enabling you to easily find the right Glecaprevir GMP manufacturer or Glecaprevir GMP API supplier for your needs.

Glecaprevir CoA

A Glecaprevir CoA (Certificate of Analysis) is a formal document that attests to Glecaprevir's compliance with Glecaprevir specifications and serves as a tool for batch-level quality control.

Glecaprevir CoA mostly includes findings from lab analyses of a specific batch. For each Glecaprevir CoA document that a company creates, the USFDA specifies specific requirements, such as supplier information, material identification, transportation data, evidence of conformity and signature data.

Glecaprevir may be tested according to a variety of international standards, such as European Pharmacopoeia (Glecaprevir EP), Glecaprevir JP (Japanese Pharmacopeia) and the US Pharmacopoeia (Glecaprevir USP).

Inform the supplier about your product requirements, specifying if you need a product with particular monograph like EP (Ph. Eur.), USP, JP, BP, or any other quality. In addition, clarify whether you need hydrochloride (HCl), anhydricum, base, micronisatum or a specific level of purity. To find reputable suppliers, utilize the filters and select those certified by GMP, FDA, or any other certification as per your requirement.
For your convenience, we have listed synonyms and CAS numbers to help you find the best supplier. The use of synonyms and CAS numbers can be helpful in identifying potential suppliers, but it is crucial to note that they might not always indicate the exact same product. It is important to confirm the product details with the supplier before making a purchase to ensure that it meets your requirements.
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