Drug Information

Drug (ID: DG01896) and It's Reported Resistant Information

• Name: EKI-285
• Synonyms: EKI-285
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Lung cancer [ICD-11: 2C25]; [1]
• Target: .; NOUNIPROTAC; [2]

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 Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Epidermal growth factor receptor (EGFR) [2]

• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung adenocarcinomas tissue; N.A.
• Experiment for Molecule Alteration: Immunoblotting analysis
• Mechanism Description: The missense mutation p.L858R (c.2573T>G) in gene EGFR cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Molecule Alteration: Missense mutation; p.L844V (c.2530C>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: HCC827EP cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: H3255DR cells; Lung; Homo sapiens (Human); CVCL_DI56
• In Vitro Model: H197 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; CytoSelect 96-well cell transformation assay

Key Molecule: Epidermal growth factor receptor (EGFR) [3]

• Molecule Alteration: Missense mutation; p.L718Q (c.2153T>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCC827 cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: PC9 cells; Lung; Homo sapiens (Human); CVCL_B260
• In Vitro Model: H3255 cells; Lung; Homo sapiens (Human); CVCL_6831
• In Vitro Model: HCC827EP cells; Lung; Homo sapiens (Human); CVCL_2063
• In Vitro Model: H3255DR cells; Lung; Homo sapiens (Human); CVCL_DI56
• In Vitro Model: H197 cells; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay; CytoSelect 96-well cell transformation assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]

• Molecule Alteration: Missense mutation; p.T798M (c.2393_2394delCAinsTG)
• Sensitive 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
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.T798M (c.2393_2394delCAinsTG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]

• Molecule Alteration: Missense mutation; p.L755S (c.2263_2264delCTinsAG)
• Sensitive 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
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755S (c.2263_2264delCTinsAG) in gene ERBB2 cause the sensitivity of EKI-285 by aberration of the drug's therapeutic target

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [4]

• Molecule Alteration: Missense mutation; p.L755P (c.2264T>C)
• Sensitive 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
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.L755P (c.2264T>C) in gene ERBB2 cause the sensitivity of EKI-285 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: Epidermal growth factor receptor (EGFR) [1]

• Molecule Alteration: Missense mutation; p.H773L (c.2318A>T)
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: NIH-H1975; N.A.; .; N.A.
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTS assay
• Mechanism Description: The missense mutation p.H773L (c.2318A>T) in gene EGFR cause the resistance of EKI-285 by aberration of the drug's therapeutic target

References

• Ref 1: Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-mutant lung cancer reveals novel treatment strategiesCancer Res. 2007 Nov 1;67(21):10417-27. doi: 10.1158/0008-5472.CAN-07-1248.
• Ref 2: Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clin Cancer Res. 2006 Nov 1;12(21):6494-501. doi: 10.1158/1078-0432.CCR-06-1570.
• Ref 3: EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR InhibitorsClin Cancer Res. 2015 Sep 1;21(17):3913-23. doi: 10.1158/1078-0432.CCR-14-2789. Epub 2015 May 6.
• Ref 4: Differential sensitivity of ERBB2 kinase domain mutations towards lapatinibPLoS One. 2011;6(10):e26760. doi: 10.1371/journal.pone.0026760. Epub 2011 Oct 28.