Drug Information

Drug (ID: DG01558) and It's Reported Resistant Information
Name
II-B08
Synonyms
1143579-78-5; II-B08; CHEMBL590043; 3-(1-(3-([1,1'-Biphenyl]-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1h-indole-5-carboxylic acid; 3-{1-[3-(biphenyl-4-ylamino)-3-oxopropyl]-1H-1,2,3-triazol-4-yl}-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic acid; 3-(1-(3-(Biphenyl-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-phenyl-1H-indole-5-carboxylic Acid; SCHEMBL13883165; II- B08; BDBM50308158; MFCD32645102; F51980; Q27461817; 3-(1-(3-([1,1'-BiPh]-4-ylamino)-3-oxopropyl)-1H-1,2,3-triazol-4-yl)-6-hydroxy-1-methyl-2-Ph-1H-indole-5-carboxylic acid; 6-hydroxy-1-methyl-3-[1-[3-oxo-3-(4-phenylanilino)propyl]triazol-4-yl]-2-phenylindole-5-carboxylic acid; JZG
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Structure
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
8
IsoSMILES
CN1C2=CC(=C(C=C2C(=C1C3=CC=CC=C3)C4=CN(N=N4)CCC(=O)NC5=CC=C(C=C5)C6=CC=CC=C6)C(=O)O)O
InChI
InChI=1S/C33H27N5O4/c1-37-28-19-29(39)26(33(41)42)18-25(28)31(32(37)23-10-6-3-7-11-23)27-20-38(36-35-27)17-16-30(40)34-24-14-12-22(13-15-24)21-8-4-2-5-9-21/h2-15,18-20,39H,16-17H2,1H3,(H,34,40)(H,41,42)
InChIKey
RATFAFAWIWHLMR-UHFFFAOYSA-N
PubChem CID
25262527
Type(s) of Resistant Mechanism of This Drug
  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
Hematologic cancer [ICD-11: 2B3Z]
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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: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
 Disease Info 
Molecule Alteration Missense mutation
p.E76K (c.226G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.70  Å
PDB: 5EHR
Mutant Type Structure Method: X-ray diffraction Resolution: 2.62  Å
PDB: 6CRF
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.04
TM score: 0.6516
Amino acid change:
E76K
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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0
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20
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30
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60
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70
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80
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90
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100
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110
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120
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130
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140
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150
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160
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170
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180
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190
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200
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210
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220
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230
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250
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280
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300
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310
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330
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380
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410
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430
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440
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510
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520
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 3H-thymidine incorporation assay
Mechanism Description The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of II-B08 by unusual activation of pro-survival pathway
References
Ref 1 Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)J Med Chem. 2010 Mar 25;53(6):2482-93. doi: 10.1021/jm901645u.

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