Drug Information

Drug (ID: DG01306) and It's Reported Resistant Information
Name
Avapritinib
Synonyms
Avapritinib; BLU-285; 1703793-34-3; Ayvakit; 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; UNII-513P80B4YJ; 513P80B4YJ; Ayvakyt; MFCD31544325; Avapritinib [INN]; Ayvakit (TN); Avapritinib (USAN/INN); Avapritinib (BLU-285); BLU-285 (Avapritinib); CHEMBL4204794; SCHEMBL16652297; GTPL10368; BLU 285; BDBM469269; AMY16753; EX-A1366; US10807985, Compound 44; NSC801082; s8553; AKOS037648993; CCG-269677; CS-7577; DB15233; NSC-801082; AC-31598; BB166456; BS-16206; HY-101561; C-366; 70C366; D11279; X720776; X-720776; Q29213676; (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; (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; (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
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Indication
In total 3 Indication(s)
Gastrointestinal stromal tumour [ICD-11: 2B5B]
Approved
[1]
Mast cell leukaemia [ICD-11: 2A21]
Approved
[1]
Systemic mastocytosis [ICD-11: 2A21]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Gastrointestinal cancer [ICD-11: 2B5B]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Gastrointestinal cancer [ICD-11: 2B5B]
[2]
Hematologic cancer [ICD-11: MG24]
[3]
Target Platelet-derived growth factor receptor alpha (PDGFRA) PGFRA_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C26H27FN10
IsoSMILES
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
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
InChIKey
DWYRIWUZIJHQKQ-SANMLTNESA-N
PubChem CID
118023034
TTD Drug ID
D0UO2P
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Gastrointestinal cancer [ICD-11: 2B5B]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]
Resistant Disease Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
 Disease Info 
Molecule Alteration Missense mutation
p.T670I (c.2009C>T)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.25  Å
PDB: 6HH1
Mutant Type Structure Method: X-ray diffraction Resolution: 2.40  Å
PDB: 8PQG
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.88
TM score: 0.9084
Amino acid change:
T670I
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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560
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580
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590
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600
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610
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630
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640
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650
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660
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670
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680
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690
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700
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750
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770
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780
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790
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800
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810
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820
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830
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840
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860
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870
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Ba/F3 cells Colon Homo sapiens (Human) CVCL_0161
M230 cells Skin Homo sapiens (Human) CVCL_D749
Experiment for
Molecule Alteration		 PCR
Experiment for
Drug Resistance		 CellTiter-Glo assay; IC50 assay
References
Ref 1 Resistance to Avapritinib in PDGFRA-Driven GIST Is Caused by Secondary Mutations in the PDGFRA Kinase Domain .Cancer Discov. 2021 Jan;11(1):108-125. doi: 10.1158/2159-8290.CD-20-0487. Epub 2020 Sep 24. 10.1158/2159-8290.CD-20-0487
Ref 2 ATP-Competitive Inhibitors Midostaurin and Avapritinib Have Distinct Resistance Profiles in Exon 17-Mutant KITCancer Res. 2019 Aug 15;79(16):4283-4292. doi: 10.1158/0008-5472.CAN-18-3139. Epub 2019 Jul 3.
Ref 3 Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignanciesBr J Haematol. 2019 Nov;187(4):488-501. doi: 10.1111/bjh.16092. Epub 2019 Jul 15.

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