Drug Information

Drug (ID: DG01523) and It's Reported Resistant Information

• Name: GDC0879
• Synonyms: GDC-0879; 905281-76-7; (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one oxime; CHEBI:83405; GDC0879; UNII-E488J6BA6E; (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one oxime; CHEMBL525191; E488J6BA6E; GDC 0879; 2-[4-[(1E)-1-hydroxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]ethanol; 2,3-dihydro-5-(1-(2-hydroxyethyl)-3-(4-pyridinyl)-1h-pyrazol-4-yl)-1h-inden-1-one oxime; 2,3-Dihydro-5-[1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl]-1H-inden-1-one oxime; 2-{4-[(1e)-1-(Hydroxyimino)-2,3-Dihydro-1h-Inden-5-Yl]-3-(Pyridin-4-Yl)-1h-Pyrazol-1-Yl}ethanol; SCHEMBL2467603; DTXSID00471110; BCPP000222; AMY20724; EX-A2357; GDC-0879,GDC0879; BDBM50029085; s1104; ZINC34640412; AKOS015856553; BCP9000714; CCG-264821; CS-0158; NCGC00263179-09; HY-50864; QC-11137; BCP0726000314; DB-000743; GDC-0879, >=98% (HPLC); X7405; EC-000.2334; J-506998; BRD-K67578145-001-01-4; BRD-K67578145-001-12-1; (E)-5-(1-(2-Hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydro-1H-inden-1-one; (E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-oneoxime; 5-(1-(2-Hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one oxime; 5-[1-(2-Hydroxy-ethyl)-3-pyridin-4-yl-1H-pyrazol-4-yl]-indan-1-one oxime; 1H-Inden-1-one, 2,3-dihydro-5-(1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl)-, oxime; 1H-Inden-1-one, 2,3-dihydro-5-(1-(2-hydroxyethyl)-3-(4-pyridinyl)-1H-pyrazol-4-yl)-, oxime, (1E)-; 2-{4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-pyridin-4-yl-1H-pyrazol-1-yl}ethanol;(E)-5-(1-(2-hydroxyethyl)-3-(pyridin-4-yl)-1H-pyrazol-4-yl)-2,3-dihydroinden-1-one oxime; 2230954-03-5
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 1; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (3 diseases)
  Colon cancer [ICD-11: 2B90]; [1]
  Lung cancer [ICD-11: 2C25]; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; [2]
• Target: Serine/threonine-protein kinase B-raf (BRAF); BRAF_HUMAN; [1]
• Formula: 4
• IsoSMILES: C1C/C(=N\\O)/C2=C1C=C(C=C2)C3=CN(N=C3C4=CC=NC=C4)CCO
• InChI: InChI=1S/C19H18N4O2/c24-10-9-23-12-17(19(21-23)13-5-7-20-8-6-13)15-1-3-16-14(11-15)2-4-18(16)22-25/h1,3,5-8,11-12,24-25H,2,4,9-10H2/b22-18+
• InChIKey: DEZZLWQELQORIU-RELWKKBWSA-N
• PubChem CID: 11717001

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 Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.F53L (c.157T>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F53L (c.157T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.Q56P (c.167A>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.K57N (c.171G>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.K57N (c.171G>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.I111S (c.332T>G)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.I111S (c.332T>G) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.C121S (c.361T>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.C121S (c.361T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.F129L (c.385T>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.F129L (c.385T>C) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Key Molecule: MAPK/ERK kinase 1 (MEK1) [2]

• Molecule Alteration: Missense mutation; p.V211D (c.632T>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEK293 cells; Kidney; Homo sapiens (Human); CVCL_0045
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: The missense mutation p.V211D (c.632T>A) in gene MAP2K1 cause the resistance of GDC0879 by unusual activation of pro-survival pathway

Colon cancer [ICD-11: 2B90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.N581Y (c.1741A>T)
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: The missense mutation p.N581Y (c.1741A>T) in gene BRAF cause the resistance of GDC0879 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: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of GDC0879 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: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.L485Y (c.1454_1455delTGinsAT)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: The missense mutation p.L485Y (c.1454_1455delTGinsAT) in gene BRAF cause the resistance of GDC0879 by aberration of the drug's therapeutic target

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of GDC0879 by aberration of the drug's therapeutic target

References

• Ref 1: Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppressionCancer Res. 2009 Apr 1;69(7):3042-51. doi: 10.1158/0008-5472.CAN-08-3563. Epub 2009 Mar 10.
• Ref 2: Increase in constitutively active MEK1 species by introduction of MEK1 mutations identified in cancersBiochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):62-70. doi: 10.1016/j.bbapap.2018.05.004. Epub 2018 May 9.