Drug Information

Drug (ID: DG01644) and It's Reported Resistant Information
Name
PLX8394
Synonyms
PLX8394; 1393466-87-9; PLX-8394; UNII-J2L7Z273SG; J2L7Z273SG; PLX 8394; (3R)-N-[3-[5-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluorophenyl]-3-fluoropyrrolidine-1-sulfonamide; (R)-N-(3-(5-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl)-3-fluoropyrrolidine-1-sulfonamide; GTPL9131; CHEMBL4303729; SCHEMBL15666953; BDBM317826; BCP19619; EX-A1461; PLX 8394;PLX8394; NSC797932; NSC801007; s7965; ZINC144705377; CS-5123; NSC-797932; NSC-801007; US9624213, Compound P-0338; NCGC00483921-01; BP168493; BS-15485; HY-18972; A16840; D83660; A900333; Q27088419; 1-Pyrrolidinesulfonamide, N-(3-((5-(2-cyclopropyl-5-pyrimidinyl)-1H-pyrrolo(2,3-b)pyridin-3-yl)carbonyl)-2,4-difluorophenyl)-3-fluoro-, (3R)-
    Click to Show/Hide
Indication
In total 1 Indication(s)
Acute myeloid leukaemia [ICD-11: 2A60]
Phase 2
[1]
Structure
Target Fms-like tyrosine kinase 3 (FLT-3) FLT3_HUMAN [2]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
7
IsoSMILES
C1CN(C[C@@H]1F)S(=O)(=O)NC2=C(C(=C(C=C2)F)C(=O)C3=CNC4=C3C=C(C=N4)C5=CN=C(N=C5)C6CC6)F
InChI
InChI=1S/C25H21F3N6O3S/c26-16-5-6-34(12-16)38(36,37)33-20-4-3-19(27)21(22(20)28)23(35)18-11-32-25-17(18)7-14(8-31-25)15-9-29-24(30-10-15)13-1-2-13/h3-4,7-11,13,16,33H,1-2,5-6,12H2,(H,31,32)/t16-/m1/s1
InChIKey
YYACLQUDUDXAPA-MRXNPFEDSA-N
PubChem CID
90116675
TTD Drug ID
D28HJI
DrugBank ID
DB16038
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  UAPP: Unusual Activation of Pro-survival Pathway
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 Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.55  Å
PDB: 4E26
Mutant Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 4G9R
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.53
TM score: 0.95765
Amino acid change:
V600E
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model PRT cells Brain Homo sapiens (Human) CVCL_7207
1205Lu cells Skin Homo sapiens (Human) CVCL_5239
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; AlamarBlue assay; Colony growth assay
References
Ref 1 Inhibition of mutant BRAF splice variant signaling by next-generation, selective RAF inhibitorsPigment Cell Melanoma Res. 2014 May;27(3):479-84. doi: 10.1111/pcmr.12218. Epub 2014 Feb 10.
Ref 2 Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF-mutant lung cancerProc Natl Acad Sci U S A. 2016 Nov 22;113(47):13456-13461. doi: 10.1073/pnas.1610456113. Epub 2016 Nov 9.

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