Drug Information

Drug (ID: DG01498) and It's Reported Resistant Information

• Name: SU11274
• Synonyms: SU11274; 658084-23-2; Met Kinase Inhibitor; SU-11274; SU 11274; PKI-SU11274; SU-MI-2; CHEMBL261641; (3Z)-N-(3-Chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; MFCD08276928; (Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide; (3Z)-N-(3-Chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; (3Z)-N-(3-Chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1H-pyrrol-2-yl]methylene]-2,3-dihydro-N-methyl-2-oxo-1H-indole-5-sulfonamide; (3z)-N-(3-Chlorophenyl)-3-({3,5-Dimethyl-4-[(4-Methylpiperazin-1-Yl)carbonyl]-1h-Pyrrol-2-Yl}methylene)-N-Methyl-2-Oxoindoline-5-Sulfonamide; (3Z)-N-(3-chlorophenyl)-3-({3,5-dimethyl-4-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-2-yl}methylidene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide; (Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(1-methylpiperazine-4-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide; (3Z)-N-(3-chlorophenyl)-3-[[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulfonamide; C28H30ClN5O4S; SCHEMBL93711; SCHEMBL93713; MLS006010961; GTPL5057; AOB6383; DTXSID20429552; EX-A183; CHEBI:190974; BCPP000061; HMS3229G21; K00593a; BDBM50341636; NSC747693; s1080; ZINC16052811; AKOS015994564; CCG-206768; ES-0032; EX-5962; NSC-747693; QC-2155; NCGC00165902-01; NCGC00165902-04; AC-28396; SMR004702765; SU-011274; SU11274 (PKI-SU11274); SU 11274, >=98% (HPLC), powder; X7471; EC-000.2357; A15738; Met Kinase Inhibitor - CAS 658084-23-2; J-522999; BRD-K02965346-001-01-8; BRD-K02965346-001-07-5; Q27088888; (3Z)-N-(3-chlorophenyl)-3-[[3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl]methylidene]-N-methyl-2-oxo-1H-indole-5-sulonamide; 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)-; N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(1-methylpiperazine-4-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide; N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(4-methylpiperazine-1-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide; N-(3-Chlorophenyl)-n-methyl-3-[[3,5-dmethyl-4-[(4-methylpperazn-1-yl)carbonyl]-1h-pyrrol-2-yl]methylene]-2-oxo-2,3-dhydro-1h-ndole-5 -sulfonamde
• Indication:
  In total 1 Indication(s)
  Discovery agent [ICD-11: N.A.]; Terminated; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [1]
• Target: Proto-oncogene c-Met (MET); MET_HUMAN; [1]
• Formula: 5
• IsoSMILES: CC1=C(NC(=C1C(=O)N2CCN(CC2)C)C)/C=C\\3/C4=C(C=CC(=C4)S(=O)(=O)N(C)C5=CC(=CC=C5)Cl)NC3=O
• InChI: InChI=1S/C28H30ClN5O4S/c1-17-25(30-18(2)26(17)28(36)34-12-10-32(3)11-13-34)16-23-22-15-21(8-9-24(22)31-27(23)35)39(37,38)33(4)20-7-5-6-19(29)14-20/h5-9,14-16,30H,10-13H2,1-4H3,(H,31,35)/b23-16-
• InChIKey: FPYJSJDOHRDAMT-KQWNVCNZSA-N
• PubChem CID: 9549297

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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [2]

• Molecule Alteration: Missense mutation; p.N375S (c.1124A>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Mechanism Description: The missense mutation p.N375S (c.1124A>G) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Molecule Alteration: Missense mutation; p.L1213V (c.3637C>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.L1213V (c.3637C>G) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Molecule Alteration: Missense mutation; p.Y1248H (c.3742T>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.Y1248H (c.3742T>C) in gene MET cause the resistance of SU11274 by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Molecule Alteration: Missense mutation; p.M1268T (c.3803T>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.M1268T (c.3803T>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [3]

• Molecule Alteration: Missense mutation; p.V1110I (c.3328G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1110I (c.3328G>A) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [3]

• Molecule Alteration: Missense mutation; p.H1112L (c.3335A>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.H1112L (c.3335A>T) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [3]

• Molecule Alteration: Missense mutation; p.V1206L (c.3616G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1206L (c.3616G>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [3]

• Molecule Alteration: Missense mutation; p.V1238I (c.3712G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.V1238I (c.3712G>A) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [2]

• Molecule Alteration: Missense mutation; p.E168D (c.504G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Mechanism Description: The missense mutation p.E168D (c.504G>C) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

Key Molecule: Hepatocyte growth factor receptor (MET) [1]

• Molecule Alteration: Missense mutation; p.H1112Y (c.3334C>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); N.A.
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.H1112Y (c.3334C>T) in gene MET cause the sensitivity of SU11274 by aberration of the drug's therapeutic target

References

• Ref 1: The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variantsOncogene. 2004 Jul 8;23(31):5387-93. doi: 10.1038/sj.onc.1207691.
• Ref 2: Ethnic differences and functional analysis of MET mutations in lung cancerClin Cancer Res. 2009 Sep 15;15(18):5714-23. doi: 10.1158/1078-0432.CCR-09-0070. Epub 2009 Sep 1.
• Ref 3: Differential inhibition sensitivities of MET mutants to the small molecule inhibitor SU11274Cancer Lett. 2010 Mar 28;289(2):228-36. doi: 10.1016/j.canlet.2009.08.017. Epub 2009 Sep 23.