Drug Information

Drug (ID: DG01495) and It's Reported Resistant Information

• Name: SU5614
• Synonyms: SU-5614; 1055412-47-9; su5614; (Z)-5-Chloro-3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one; CHEMBL2062155; CHEBI:87159; 186611-56-3; SU 5614; (Z)-SU5614; AC1NS4RE; (3Z)-5-chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one; (3Z)-5-Chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylene]-1,3-dihydro-2H-indol-2-one; MFCD08443928; 5-Chloro-3-[(3,5-dimethylpyrrol-2-yl)methylene]-2-indolinone; 5-CHLORO-3-(3,5-DIMETHYL-1H-PYRROL-2-YLMETHYLENE)-1,3-DIHYDRO-INDOL-2-ONE; EX-A821; ZINC3875026; BDBM50415432; HY-18952A; AKOS030527565; CID:6536806; NCGC00480782-01; AS-70968; DS-019384; SU5614, >=98% (HPLC); CS-0029269; A895990; J-690017; Q27159416; 5-chloro-3-((3,5-dimethyl-1H-pyrrol-2-yl)methylene)indolin-2-one; 5-chloro-3-(3,5-dimethyl-1h-pyrrol-2-ylmethylene)-1,3-dihydroindol-2-one; (3Z)-5-chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one; (3Z)-5-chloro-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-2,3-dihydro-1H-indol-2-one; 3-Chloro-N-[(1S)-2-[[2-(dimethylamino)acetyl]amino]-1-[[4-[8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl]phenyl]methyl]ethyl]-4- (1-methylethoxy)-benzamide
• Indication:
  In total 2 Indication(s)
  Breast cancer [ICD-11: 2C60]; Terminated; [1]
  Multiple myeloma [ICD-11: 2A83]; Terminated; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Acute myeloid leukemia [ICD-11: 2A60]; [2]
• Target: Heat shock protein 90 alpha (HSP90A); HS90A_HUMAN; [2]
• Formula: 1
• IsoSMILES: CC1=CC(=C(N1)/C=C\\2/C3=C(C=CC(=C3)Cl)NC2=O)C
• InChI: InChI=1S/C15H13ClN2O/c1-8-5-9(2)17-14(8)7-12-11-6-10(16)3-4-13(11)18-15(12)19/h3-7,17H,1-2H3,(H,18,19)/b12-7-
• InChIKey: XLBQNZICMYZIQT-GHXNOFRVSA-N
• PubChem CID: 6536806
• ChEBI ID: CHEBI:87159
• TTD Drug ID: D0SC2J

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

Acute myeloid leukemia [ICD-11: 2A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [2]

• Molecule Alteration: IF-deletion; p.Q569_G613 (c.1705_1837)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The if-deletion p.Q569_G613 (c.1705_1837) in gene FLT3 cause the resistance of SU5614 by unusual activation of pro-survival pathway.

Key Molecule: Receptor-type tyrosine-protein kinase FLT3 (FLT3) [1]

• Molecule Alteration: Missense mutation; p.D835Y (c.2503G>T)
• Resistant Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: The missense mutation p.D835Y (c.2503G>T) in gene FLT3 cause the resistance of SU5614 by unusual activation of pro-survival pathway

References

• Ref 1: FMS-like tyrosine kinase 3-internal tandem duplication tyrosine kinase inhibitors display a nonoverlapping profile of resistance mutations in vitroCancer Res. 2009 Apr 1;69(7):3032-41. doi: 10.1158/0008-5472.CAN-08-2923. Epub 2009 Mar 24.
• Ref 2: FLT3-ITD-TKD dual mutants associated with AML confer resistance to FLT3 PTK inhibitors and cytotoxic agents by overexpression of Bcl-x(L)Blood. 2005 May 1;105(9):3679-85. doi: 10.1182/blood-2004-06-2459. Epub 2004 Dec 30.