Drug (ID: DG01577) and It's Reported Resistant Information
Name
Flumatinib
Synonyms
Flumatinib; 895519-90-1; HHGV678; HH-GV678; Flumatinib free base; flumbatinib; UNII-R4009Y24AI; HHGV-678; R4009Y24AI; 895519-90-1 (free base); 4-[(4-methylpiperazin-1-yl)methyl]-N-[6-methyl-5-[(4-pyridin-3-ylpyrimidin-2-yl)amino]pyridin-3-yl]-3-(trifluoromethyl)benzamide; HHGV678 mesylate; BenzaMide, 4-[(4-Methyl-1-piperazinyl)Methyl]-N-[6-Methyl-5-[[4-(3-pyridinyl)-2-pyriMidinyl]aMino]-3-pyridinyl]-3-(trifluoroMethyl)-; N-(6-methyl-5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)pyridin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide; HH-GV-678; Hansoh Xinfu; flumatinib (pseudo INN); GTPL9913; SCHEMBL4883843; CHEMBL3545413; DTXSID60237779; BCP23797; EX-A3572; VKB51990; BDBM50529313; NSC830368; ZINC68244727; CS-5550; DB11904; NSC-830368; SB17192; NCGC00378614-01; 4-(4-Methylpiperazin-1-ylmethyl)-N-(6-methyl-5-(4-pyridin-3-ylpyrimidin-2-ylamino)pyridin-3-yl)-3-trifluoromethylbenzamide; DA-33625; HY-13904; FT-0739882; Q27287759; N-[5-[[4-(3-Pyridinyl)pyrimidine-2-yl]amino]-6-methylpyridine-3-yl]-3-(trifluoromethyl)-4-[(4-methylpiperazine-1-yl)methyl]benzamide
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Indication
In total 3 Indication(s)
leukaemia [ICD-11: 2A60-2B33]
Phase 2
[1]
Multiple myeloma [ICD-11: 2A83]
Phase 2
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 2
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Target RAC-alpha serine/threonine-protein kinase (AKT1) AKT1_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
7
IsoSMILES
CC1=C(C=C(C=N1)NC(=O)C2=CC(=C(C=C2)CN3CCN(CC3)C)C(F)(F)F)NC4=NC=CC(=N4)C5=CN=CC=C5
InChI
InChI=1S/C29H29F3N8O/c1-19-26(38-28-34-9-7-25(37-28)21-4-3-8-33-16-21)15-23(17-35-19)36-27(41)20-5-6-22(24(14-20)29(30,31)32)18-40-12-10-39(2)11-13-40/h3-9,14-17H,10-13,18H2,1-2H3,(H,36,41)(H,34,37,38)
InChIKey
BJCJYEYYYGBROF-UHFFFAOYSA-N
PubChem CID
46848036
TTD Drug ID
D02NXM
DrugBank ID
DB11904
Type(s) of Resistant Mechanism of This Drug
  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
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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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) [1]
Molecule Alteration Duplication
p.I571_D579 (c.1711_1737)
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The duplication p.I571_D579 (c.1711_1737) in gene KIT cause the resistance of Flumatinib by aberration of the drug's therapeutic target.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Missense mutation
p.D816Y (c.2446G>T)
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model IL-3-dependent murine hematopoietic cells Blood Mus musculus (Mouse) CVCL_2015
IL-3-dependent murine hematopoietic cells Blood Mus musculus (Mouse) CVCL_2015
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Missense mutation
p.D816V (c.2447A>T)
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model IL-3-dependent murine hematopoietic cells Blood Mus musculus (Mouse) CVCL_2015
IL-3-dependent murine hematopoietic cells Blood Mus musculus (Mouse) CVCL_2015
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Drug Sensitivity 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) [1]
Molecule Alteration Complex-indel
p.T417_D419delinsI (c.1249_1257delinsATC)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The complex-indel p.T417_D419delinsI (c.1249_1257delinsATC) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Duplication
p.A502_Y503 (c.1504_1509)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The duplication p.A502_Y503 (c.1504_1509) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration IF-deletion
p.V559_V560delVV (c.1676_1681delTTGTTG)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The if-deletion p.V559_V560delVV (c.1676_1681delTTGTTG) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Missense mutation
p.N822K (c.2466T>G)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The missense mutation p.N822K (c.2466T>G) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Missense mutation
p.V559D (c.1676T>A)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The missense mutation p.V559D (c.1676T>A) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [1]
Molecule Alteration Missense mutation
p.D816H (c.2446G>C)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model 32D cells Bone marrow Homo sapiens (Human) CVCL_0118
In Vivo Model Female Balb/cA-nu/nu mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The missense mutation p.D816H (c.2446G>C) in gene KIT cause the sensitivity of Flumatinib by aberration of the drug's therapeutic target
References
Ref 1 Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutantsCancer Sci. 2014 Jan;105(1):117-25. doi: 10.1111/cas.12320. Epub 2014 Jan 4.

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