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Chemistry

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Also known as: Blu-285, 1703793-34-3, Ayvakit, Avapritinib [inn], Blu285, (1s)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
Molecular Formula
C26H27FN10
Molecular Weight
498.6  g/mol
InChI Key
DWYRIWUZIJHQKQ-SANMLTNESA-N
FDA UNII
513P80B4YJ

Avapritinib
Avapritinib is an orally bioavailable inhibitor of specific mutated forms of platelet-derived growth factor receptor alpha (PDGFR alpha; PDGFRa) and mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, avapritinib specifically binds to and inhibits specific mutant forms of PDGFRa and c-Kit, including the PDGFRa D842V mutant and various KIT exon 17 mutants. This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants. PDGFRa and c-Kit, protein tyrosine kinases and tumor-associated antigens (TAAs), are mutated in various tumor cell types; they play key roles in the regulation of cellular proliferation.
Avapritinib is a Kinase Inhibitor. The mechanism of action of avapritinib is as a Tyrosine Kinase Inhibitor, and Cytochrome P450 2C9 Inhibitor, and P-Glycoprotein Inhibitor, and Breast Cancer Resistance Protein Inhibitor, and Multidrug and Toxin Extrusion Transporter 1 Inhibitor, and Multidrug and Toxin Extrusion Transporter 2 K Inhibitor, and Bile Salt Export Pump Inhibitor.
1 2D Structure

Avapritinib

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
(1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine
2.1.2 InChI
InChI=1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
2.1.3 InChI Key
DWYRIWUZIJHQKQ-SANMLTNESA-N
2.1.4 Canonical SMILES
CC(C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
2.1.5 Isomeric SMILES
C[C@](C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
2.2 Other Identifiers
2.2.1 UNII
513P80B4YJ
2.3 Synonyms
2.3.1 MeSH Synonyms

1. (1s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)-1-piperazinyl)-5-pyrimidinyl)ethanamine

2. 5-pyrimidinemethanamine, Alpha-(4-fluorophenyl)-alpha-methyl-2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)-1-piperazinyl)-, (alphas)-

3. Ayvakit

4. Blu-285

2.3.2 Depositor-Supplied Synonyms

1. Blu-285

2. 1703793-34-3

3. Ayvakit

4. Avapritinib [inn]

5. Blu285

6. (1s)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl]pyrimidin-5-yl]ethanamine

7. 513p80b4yj

8. C-366

9. 70c366

10. X720776

11. X-720776

12. Ayvakyt

13. Mfcd31544325

14. Ayvakit (tn)

15. Avapritinib [mi]

16. Avapritinib (usan/inn)

17. Avapritinib [usan]

18. Avapritinib (blu-285)

19. Blu-285 (avapritinib)

20. Avapritinib [who-dd]

21. Unii-513p80b4yj

22. Chembl4204794

23. Schembl16652297

24. Gtpl10368

25. Avapritinib [orange Book]

26. Blu 285

27. Bdbm469269

28. Dtxsid301027935

29. Amy16753

30. Ex-a1366

31. Us10807985, Compound 44

32. Nsc801082

33. S8553

34. Akos037648993

35. Ccg-269677

36. Cs-7577

37. Db15233

38. Nsc-801082

39. (s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethan-1-amine

40. Ac-31598

41. Bb166456

42. Bs-16206

43. Hy-101561

44. D11279

45. Q29213676

46. (1s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)-1-piperazinyl)-5-pyrimidinyl)ethanamine

47. (1s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethan-1-amine

48. (s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)piperazin-yl)pyrimidin-5-yl)ethan-1-amine

49. (s)-1-(4-fluorophenyl)-1-(2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl)piperazin-1-yl)pyrimidin-5-yl)ethanamine

50. 5-pyrimidinemethanamine, .alpha.-(4-fluorophenyl)-.alpha.-methyl-2-(4-(6-(1-methyl-1h-pyrazol-4-yl)pyrrolo(2,1-f)(1,2,4)triazin-4-yl)-1-piperazinyl)-, (.alpha.s)-

2.4 Create Date
2016-02-23
3 Chemical and Physical Properties
Molecular Weight 498.6 g/mol
Molecular Formula C26H27FN10
XLogP31.9
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count9
Rotatable Bond Count5
Exact Mass498.24041907 g/mol
Monoisotopic Mass498.24041907 g/mol
Topological Polar Surface Area106 Ų
Heavy Atom Count37
Formal Charge0
Complexity752
Isotope Atom Count0
Defined Atom Stereocenter Count1
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Avapritinib is indicated for the treatment of unresectable, metastatic gastrointestinal stromal tumors with a platelet-derived growth factor receptor alpha exon 18 mutation.


Treatment of mastocytosis


Treatment of all conditions included in the category of malignant neoplasms (except haematopoietic and lymphoid tissue neoplasms)


Ayvakyt is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumours (GIST) harbouring the platelet-derived growth factor receptor alpha (PDGFRA) D842V mutation.


5 Pharmacology and Biochemistry
5.1 Pharmacology

Avapritinib is a selective kinase inhibitor that negatively modulates the action of cell transporters to resensitize them to other chemotherapies. It has a long duration of action as it is given once daily. Patients should be counselled regarding the risk of intracranial hemorrhage, CNS effects, and embryo-fetal toxicity.


5.2 FDA Pharmacological Classification
5.2.1 Active Moiety
AVAPRITINIB
5.2.2 FDA UNII
513P80B4YJ
5.2.3 Pharmacological Classes
Breast Cancer Resistance Protein Inhibitors [MoA]; Cytochrome P450 2C9 Inhibitors [MoA]; Kinase Inhibitor [EPC]; Multidrug and Toxin Extrusion Transporter 1 Inhibitors [MoA]; Multidrug and Toxin Extrusion Transporter 2 K Inhibitors [MoA]; P-Glycoprotein Inhibitors [MoA]; Tyrosine Kinase Inhibitors [MoA]; Bile Salt Export Pump Inhibitors [MoA]
5.3 ATC Code

L01EX18


L - Antineoplastic and immunomodulating agents

L01 - Antineoplastic agents

L01E - Protein kinase inhibitors

L01EX - Other protein kinase inhibitors

L01EX18 - Avapritinib


5.4 Absorption, Distribution and Excretion

Absorption

A 300mg oral dose of avapritinib reaches a Cmax of 813ng/mL with a Tmax of 2.0-4.1h and an AUC of 15400h\*ng/mL.


Route of Elimination

Avapritinib is 70% eliminated in the feces with 11% as the unchanged drug and 18% eliminated in the urine with 0.23% as the unchanged drug.


Volume of Distribution

The mean apparent volume of distribution is 1200L.


Clearance

The mean apparent oral clearance of avapritinib is 19.5L/h.


5.5 Metabolism/Metabolites

Avapritinib is metabolized mainly by CYP3A4 and CYP2C9 in vitro. A 310mg oral dose is recovered as 49% unchanged drug, 35% hydroxy glucuronide metabolite, and 14% oxidatively deaminated metabolite.


5.6 Biological Half-Life

The half life of avapritinib is 32-57h.


5.7 Mechanism of Action

Avapritinib has a negative modulating effect on the transporters ABCB1 and ABCG2, which mediate the multidrug resistance phenotype of some cancers. This modulation may be due to interactions of avapritinib with the drug binding pocket of these transporters. Negative modulation of these transporters, resensitizes cancerous cells to treatment with chemotherapeutic agents like [paclitaxel].


Listed Suppliers

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Virtual BoothEgis is a Hungarian generic pharma company with 110 years history. Our activities incorporate all areas of the pharma value chain.

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Avapritinib

About the Company : Egis is a member of the Servier Group. Egis’ products are manufactured at 3 production sites in Hungary, which are certified by EMA,FDA, ANVISA, PMDA ,KFDA. Egis sells its produc...

Egis is a member of the Servier Group. Egis’ products are manufactured at 3 production sites in Hungary, which are certified by EMA,FDA, ANVISA, PMDA ,KFDA. Egis sells its products under Egis’ brand names in 18 countries. In total, the company’s APIs & finished products reach 100 countries. Egis’ focus lies on treating diseases of cardiovascular & central nervous systems; however, it also provides modern treatment solutions in the fields of diabetology, dermatology & wound care. Our research and development activities focus on high-quality, value-added branded generic products. From 2023, Egis offers its CDMO & CMO services as well.
Egis Pharmaceuticals

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Virtual BoothTAPI offers customized CDMO Solutions for API development and manufacturing services.

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Avapritinib

About the Company : Founded in 1935, TAPI Technology & API Services has a long-standing tradition of advancing health through innovation and dedication. Today, we proudly build upon this legacy, drivi...

Founded in 1935, TAPI Technology & API Services has a long-standing tradition of advancing health through innovation and dedication. Today, we proudly build upon this legacy, driving progress in the pharmaceutical industry. Leveraging our extensive experience and world-class expertise, we deliver one of the most comprehensive API portfolios in the industry. Additionally, we provide tailored CDMO services, harnessing our proficiency in diverse technologies to meet our partners' unique needs, ensuring flexibility and excellence in every project.
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Avapritinib

About the Company : Beijing Sjar Technology Development Co., Ltd. founded in 2014, it is a high-tech enterprise which specialized in the research and development of active pharmaceutical ingredients a...

Beijing Sjar Technology Development Co., Ltd. founded in 2014, it is a high-tech enterprise which specialized in the research and development of active pharmaceutical ingredients and their intermediates, electronic chemical materials and intermediates, large-scale production, sales and services, and provide customized synthetic services according to customer requirements. Sjar-Tech locates in Beijing Economic and Technological Development Zone, has its own R&D and development laboratory. Sjar-Tech has set up a R&D team with rich experience and strong technical strength, most of the practitioners have more than ten years' experience.
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ABOUT THIS PAGE

Avapritinib Manufacturers

A Avapritinib manufacturer is defined as any person or entity involved in the manufacture, preparation, processing, compounding or propagation of Avapritinib, including repackagers and relabelers. The FDA regulates Avapritinib manufacturers to ensure that their products comply with relevant laws and regulations and are safe and effective to use. Avapritinib 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 Avapritinib manufacturers with USDMF, JDMF, KDMF, CEP, GMP, COA and API Price related information on PhamaCompass.

Avapritinib Suppliers

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

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

Avapritinib GMP

Avapritinib 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 Avapritinib 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 Avapritinib GMP manufacturer or Avapritinib GMP API supplier for your needs.

Avapritinib CoA

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

Avapritinib CoA mostly includes findings from lab analyses of a specific batch. For each Avapritinib 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.

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