Drug Information

Drug (ID: DG01541) and It's Reported Resistant Information

• Name: BMS-777607
• Synonyms: BMS-777607; 1025720-94-8; BMS 777607; 1196681-44-3; BMS777607; ASLAN-002; UNII-A3MMS6HDO1; ASLAN002; N-(4-(2-Amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; A3MMS6HDO1; N-[4-(2-amino-3-chloropyridin-4-yl)oxy-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxopyridine-3-carboxamide; BMS 817378; 3-Pyridinecarboxamide, N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-1,2-dihydro-2-oxo-; N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-[4-[(2-Amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-{4-[(2-amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl}-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; 3-Pyridinecarboxamide, N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-1,2-dihydro-2-oxo-;3-Pyridinecarboxamide, N-[4-[(2-amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-1,2-dihydro-2-oxo-; N-(4-((2-amino-3-chloropyridin-4-yl)oxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide.; MLS006010958; C25H19ClF2N4O4; CHEMBL460702; GTPL7953; SCHEMBL2588311; BDBM28031; CHEBI:91409; DTXSID50145278; EX-A004; 3f82; HMS3295I07; HMS3655C05; AMY24190; AOB87395; BCP02303; BCP13190; BMS777606; MFCD16495773; NSC764090; NSC799365; s1561; ZINC39716080; AKOS026750587; BCP9000432; CCG-264913; CS-0227; DB12064; EX-7213; NSC-764090; NSC-799365; QC-7244; SB16607; NCGC00263157-01; NCGC00263157-09; AC-30912; AC-31421; AS-17034; DA-35016; HY-12076; N-[4-[(2-Amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-1,2-dihydro-2-oxo-3-pyridinecarboxamide; N-{4-[(2-Amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl}-4-ethoxy -1-(4-fluorophenyl)-2-oxo-1,2-dihydro-3-pyridinecarboxamide; SMR004702762; BMS-777607;BMS777607; FT-0701277; FT-0722977; SW219298-1; X7495; A25030; BMS-777607, >=98% (HPLC); J-004169; J-523337; BRD-K40738845-001-01-9; Q27075371; N-(4-(2-amino-3-chloropyridin-4-yloxy )-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide; N-[4-[(2-Amino-3-chloro-4-pyridinyl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-1,2-dihydro-2-oxo-3-pyridinecarboxamide,; N-[4-[(2-Amino-3-chloropyridin-4-yl)oxy]-3-fluorophenyl]-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide;BMS-817378;BMS-777607
• Indication:
  In total 6 Indication(s)
  Breast cancer [ICD-11: 2C60]; Phase 1/2; [1]
  Colorectal cancer [ICD-11: 2B91]; Phase 1/2; [1]
  Gastric adenocarcinoma [ICD-11: 2B72]; Phase 1/2; [1]
  Prostate cancer [ICD-11: 2C82]; Phase 1/2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1/2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1/2; [1]
• Target: RAC-alpha serine/threonine-protein kinase (AKT1); AKT1_HUMAN; [1]
• Formula: 7
• IsoSMILES: CCOC1=C(C(=O)N(C=C1)C2=CC=C(C=C2)F)C(=O)NC3=CC(=C(C=C3)OC4=C(C(=NC=C4)N)Cl)F
• InChI: InChI=1S/C25H19ClF2N4O4/c1-2-35-19-10-12-32(16-6-3-14(27)4-7-16)25(34)21(19)24(33)31-15-5-8-18(17(28)13-15)36-20-9-11-30-23(29)22(20)26/h3-13H,2H2,1H3,(H2,29,30)(H,31,33)
• InChIKey: VNBRGSXVFBYQNN-UHFFFAOYSA-N
• PubChem CID: 24794418
• ChEBI ID: CHEBI:91409
• TTD Drug ID: D0I4TH
• DrugBank ID: DB12064

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

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

Epigenetic Alteration of DNA, RNA or Protein (EADR)

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

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.Y1230H (c.3688T>C)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 1.71 Å; PDB: 5HNI
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 1.97 Å; PDB: 5HLW

RMSD: 0.65; TM score: 0.96625; Amino acid change: Y1230H

• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); CVCL_0594
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

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

• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Molecule Alteration: Missense mutation; p.D1228N (c.3682G>A)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NIH3T3 cells; Embryo; Homo sapiens (Human); CVCL_0594
• In Vivo Model: Athymic female mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: MET mutations Y1248H and D1246N are resistance mechanisms for type I MET-TKIs. NIH3T3 cells expressing either mutation showed resistance to both INC280 and crizotinib but not cabozantinib, indicating the potential of sequential use of MET inhibitors may lead to a more durable response.

References

• Ref 1: Acquired MET Y1248H and D1246N Mutations Mediate Resistance to MET Inhibitors in Non-Small Cell Lung CancerClin Cancer Res. 2017 Aug 15;23(16):4929-4937. doi: 10.1158/1078-0432.CCR-16-3273. Epub 2017 Apr 10.