Drug Information

Drug (ID: DG01563) and It's Reported Resistant Information

• Name: Foretinib
• Synonyms: Foretinib; 849217-64-7; GSK1363089; XL880; EXEL-2880; Foretinib (GSK1363089); XL-880; GSK 1363089; XL 880; GSK089; EXEL 2880; GSK-1363089; UNII-81FH7VK1C4; 81FH7VK1C4; GSK-089; GSK1363089G; 937176-80-2; N-[3-Fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide; C34H34F2N4O6; 88Z; n-(3-fluoro-4-((6-methoxy-7-(3-(4-morpholinyl)propoxy)-4-quinolinyl)oxy)phenyl)-n'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide; N-(3-Fluoro-4-{[6-Methoxy-7-(3-Morpholin-4-Ylpropoxy)quinolin-4-Yl]oxy}phenyl)-N'-(4-Fluorophenyl)cyclopropane-1,1-Dicarboxamide; N-[3-fluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; N-(3-Fluoro-4-((6-methoxy-7-(3-(morpholin-4-yl)propoxy)quinolin-4-yl)oxy)phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl]oxy)phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; Foretinib(XL880); xl-880, Foretinib; Foretinib (USAN/INN); Foretinib [USAN:INN]; MLS006010302; SCHEMBL371804; Foretinib - GSK1363089; GTPL5679; QCR-49; CHEMBL1230609; CHEBI:91418; AOB6031; DTXSID20918193; EX-A050; SYN1129; BCPP000236; HMS3295K13; HMS3654G04; BCP02231; BDBM50399540; GSK 1363089G; GSK-1363089G; MFCD16038048; NSC755775; NSC800101; s1111; ZINC43204048; Foretinib,XL880, GSK1363089; AKOS015904319; BCP9000675; CCG-270292; CS-0153; DB12307; NSC-755775; NSC-800101; PB27007; SB20469; Foretinib (GSK1363089, XL880); NCGC00263104-01; NCGC00263104-10; AC-25081; AS-16268; HY-10338; SMR003599144; SW219390-1; W8766; EC-000.2326; A25642; D09618; XL880, GSK1363089G, Exel 2880; J-523004; Q5469311; BRD-K03449891-001-01-1; 1,1-Cyclopropanedicarboxamide, N-(3-fluoro-4-((6-methoxy-7-(3-(4-morpholinyl)propoxy)-4-quinolinyl)oxy)phenyl)-N'-(4-fluorophenyl)-; 1-N'-[3-fluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; 1-N'-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; GSK1363089;EXEL-2880;Foretinib;N-[3-Fluoro-4-[[6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-quinolinyl]oxy]phenyl]-N'-(4-fluorophenyl)-1,1-cyclopropanedicarboxamide;Foretinib; N-(4-(7-(3-MORPHOLINOPROPOXY)-6-METHOXYQUINOLIN-4-YLOXY)-3-FLUOROPHENYL)-N-(4-FLUOROPHENYL)CYCLOPROPANE-1,1-DICARBOXAMIDE; N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin 4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide; N-[3-Fluoro-4-({6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinolin-4-yl}oxy)phenyl]-1-[(4-fluorophenyl)carbamoyl]cyclopropane-1-carboximidic acid
• Indication:
  In total 1 Indication(s)
  Clostridium infection [ICD-11: 1A04]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [1]
• Target: .; NOUNIPROTAC; [2]
• Formula: 12
• IsoSMILES: COC1=CC2=C(C=CN=C2C=C1OCCCN3CCOCC3)OC4=C(C=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F
• InChI: InChI=1S/C34H34F2N4O6/c1-43-30-20-25-27(21-31(30)45-16-2-13-40-14-17-44-18-15-40)37-12-9-28(25)46-29-8-7-24(19-26(29)36)39-33(42)34(10-11-34)32(41)38-23-5-3-22(35)4-6-23/h3-9,12,19-21H,2,10-11,13-18H2,1H3,(H,38,41)(H,39,42)
• InChIKey: CXQHYVUVSFXTMY-UHFFFAOYSA-N
• PubChem CID: 42642645
• ChEBI ID: CHEBI:91418
• TTD Drug ID: D08VWO
• DrugBank ID: DB12307

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

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

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein kinase ABL1 (ABL1) [2]

• Molecule Alteration: Missense mutation; p.V299L (c.895G>C)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ph+ALL cells; N.A.; .; N.A.
• Mechanism Description: The missense mutation p.V299L (c.895G>C) in gene ABL1 cause the sensitivity of Foretinib by aberration of the drug's therapeutic target

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene c-Ros (ROS1) [1]

• Molecule Alteration: Missense mutation; p.L2155S (c.6464T>C)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• Experiment for Molecule Alteration: Western blotting analysis; EGFR signaling antibody array; Quantitative real-time PCR; RNA-seq
• Experiment for Drug Resistance: CellTiter-Glo assay

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Proto-oncogene c-Ros (ROS1) [1]

• Molecule Alteration: Missense mutation; p.G2032R (c.6094G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• In Vitro Model: H3122 cells; Lung; Homo sapiens (Human); CVCL_5160
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter96 Aqueous One Solution assay; IC50 assay

Key Molecule: Proto-oncogene c-Ros (ROS1) [1]

• Molecule Alteration: Missense mutation; p.L2026M (c.6076C>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• Experiment for Molecule Alteration: Western blotting analysis; EGFR signaling antibody array; Quantitative real-time PCR; RNA-seq
• Experiment for Drug Resistance: CellTiter-Glo assay

Key Molecule: Proto-oncogene c-Ros (ROS1) [1]

• Molecule Alteration: Missense mutation; p.G2101A (c.6302G>C)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vitro Model: HCC78 cells; Pleural effusion; Homo sapiens (Human); CVCL_2061
• Experiment for Molecule Alteration: Western blotting analysis; EGFR signaling antibody array; qPCR; RNA-seq
• Experiment for Drug Resistance: CellTiter-Glo assay

References

• Ref 1: Molecular Changes Associated with Acquired Resistance to Crizotinib in ROS1-Rearranged Non-Small Cell Lung CancerClin Cancer Res. 2015 May 15;21(10):2379-87. doi: 10.1158/1078-0432.CCR-14-1350. Epub 2015 Feb 16.
• Ref 2: Exploiting Temporal Collateral Sensitivity in Tumor Clonal EvolutionCell. 2016 Mar 24;165(1):234-246. doi: 10.1016/j.cell.2016.01.045. Epub 2016 Feb 25.