avapritinib   Click here for help

GtoPdb Ligand ID: 10368

Synonyms: Ayvakit® | Ayvakyt® | BLU-285 | BLU285
Approved drug Immunopharmacology Ligand
avapritinib is an approved drug (FDA & EMA (2020))
Compound class: Synthetic organic
Comment: Avapritinib (BLU-285) was developed by Blueprint Medicines as an oral precision therapy to selectively and potently inhibit KIT and PDGFRA mutant kinases [3]. It is a Type I kinase inhibitor that binds the active kinase conformation. Avapritinib binds to the 'switch pocket' of KIT, a domain that regulates the enzyme's catalytic conformation. Compounds that act in this way are often referred to as switch control inhibitors [1]. Another such switch control inhibitor is ripretinib.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 106.29
Molecular weight 498.24
XLogP 4.21
No. Lipinski's rules broken 0
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Canonical SMILES Fc1ccc(cc1)C(c1cnc(nc1)N1CCN(CC1)c1ncnn2c1cc(c2)c1cnn(c1)C)(N)C
Isomeric SMILES Fc1ccc(cc1)[C@@](c1cnc(nc1)N1CCN(CC1)c1ncnn2c1cc(c2)c1cnn(c1)C)(N)C
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
1. Bai Y, Bandara G, Ching Chan E, Maric I, Simakova O, Bandara SN, Lu WP, Wise SC, Flynn DL, Metcalfe DD et al.. (2013)
Targeting the KIT activating switch control pocket: a novel mechanism to inhibit neoplastic mast cell proliferation and mast cell activation.
Leukemia, 27 (2): 278-85. [PMID:22907049]
2. Dhillon S. (2020)
Avapritinib: First Approval.
Drugs, 80 (4): 433-439. [PMID:32100250]
3. Evans EK, Gardino AK, Kim JL, Hodous BL, Shutes A, Davis A, Zhu XJ, Schmidt-Kittler O, Wilson D, Wilson K et al.. (2017)
A precision therapy against cancers driven by KIT/PDGFRA mutations.
Sci Transl Med, 9 (414). [PMID:29093181]
4. Gotlib J. (2017)
A molecular roadmap for midostaurin in mastocytosis.
Blood, 130 (2): 98-100. [PMID:28705853]
5. Mazzocca A, Napolitano A, Silletta M, Spalato Ceruso M, Santini D, Tonini G, Vincenzi B. (2019)
New frontiers in the medical management of gastrointestinal stromal tumours.
Ther Adv Med Oncol, 11. DOI: 10.1177/1758835919841946 [PMID:31205499]
6. (2017)
BLU-285, DCC-2618 Show Activity against GIST.
Cancer Discov, 7 (2): 121-122. [PMID:28077435]
7. (2018)
Rapid Responses to Avapritinib (BLU-285) in Mastocytosis.
Cancer Discov, 8 (2): 133. [PMID:29233825]