Drug Information

Drug (ID: DG01214) and It's Reported Resistant Information

• Name: Dacomitinib
• Synonyms: Dacomitinib; 1110813-31-4; PF299804; Dacomitinib (PF299804, PF299); PF-00299804; UNII-2XJX250C20; (2E)-N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxy-6-quinazolinyl]-4-(1-piperidinyl)-2-butenamide; (E)-N-(4-((3-chloro-4-fluorophenyl)aMino)-7-Methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enaMide; 2XJX250C20; PF 00299804-03; Vizimpro; PF-299804; PF-00299804-03; (E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide; C24H25ClFN5O2; (2e)-N-{4-[(3-Chloro-4-Fluorophenyl)amino]-7-Methoxyquinazolin-6-Yl}-4-(Piperidin-1-Yl)but-2-Enamide; Dacomitinib [USAN:INN]; dacomitinibum; PF299; (E)-N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl]-4-(piperidin-1-yl)but-2-enamide; Dacomitinib (INN); Dacomitinib anhydrous; Dacomitinib (PF299804); MLS006011275; GTPL7422; CHEMBL2110732; PF-00299804 dacomitinib; CHEBI:91466; DTXSID50149493; EX-A030; QCR-174; CHEBI:132268; BDBM112499; Dacomitinib (PF-00299804); AMY21292; AOB87383; AOB87735; BCP02530; MFCD19443734; NSC765888; NSC800084; PF-299; s2727; ZINC72266312; AKOS025401818; CCG-264987; CS-0500; DB11963; NSC-765888; NSC-800084; US8623883, No. 2; NCGC00263185-09; NCGC00263185-10; AC-25915; AS-57686; HY-13272; SMR004703025; PF299804; ; ; PF299; D5450; SW219155-1; Y0338; D09883; Dacomitinib (PF299804, PF-00299804); PF-299804 (Dacomitinib PF-00299804); J-500784; Q17130597; (2E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-(piperidin-1-yl)but-2-enamide; (E)-N-(4-(3-Chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yl)-4-(piperidin-1-yl)but-2-enamide; (E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide; 2-Butenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-methoxy-6-quinazolinyl)-4-(1-piperidinyl)-, (2E)-
• Indication:
  In total 3 Indication(s)
  Non-small-cell lung cancer [ICD-11: 2C25]; Approved; [1]
  Non-small-cell lung cancer [ICD-11: 2C25]; Approved; [1]
  Non-small-cell lung cancer [ICD-11: 2C25]; Approved; [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]; [3]
• Target: Epidermal growth factor receptor (EGFR); EGFR_HUMAN; [1]
• Target: Erbb2 tyrosine kinase receptor (HER2); ERBB2_HUMAN; [1]
• Target: Erbb4 tyrosine kinase receptor (Erbb-4); ERBB4_HUMAN; [1]
• Formula: C24H25ClFN5O2
• IsoSMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4
• InChI: 1S/C24H25ClFN5O2/c1-33-22-14-20-17(24(28-15-27-20)29-16-7-8-19(26)18(25)12-16)13-21(22)30-23(32)6-5-11-31-9-3-2-4-10-31/h5-8,12-15H,2-4,9-11H2,1H3,(H,30,32)(H,27,28,29)/b6-5+
• InChIKey: LVXJQMNHJWSHET-AATRIKPKSA-N
• PubChem CID: 11511120
• ChEBI ID: CHEBI:91466
• TTD Drug ID: D06XXH
• VARIDT ID: DR00109
• INTEDE ID: DR0407
• DrugBank ID: DB11963

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: Epidermal growth factor receptor (EGFR) [2]

• Molecule Alteration: IF-insertion; p.Y764_V765insHH (c.2292_2293insCATCAT)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: Duplication; p.A767_V769 (c.2299_2307)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: Duplication; p.S768_D770 (c.2302_2310)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Duplication; p.Y772_A775 (c.2314_2325)
• Resistant 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
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

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: Complex-indel; p.D770_770delinsGY (c.2308_2310delinsGGTTAT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: Complex-indel; p.M774_774delinsWLV (c.2320_2322delinsTGGCTTGTA)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: IF-insertion; p.G778_S779insCPG (c.2335_2336insGTCCTGGTT)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Epidermal growth factor receptor (EGFR) [4]

• Molecule Alteration: Missense mutation; p.E709K (c.2125G>A)
• 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: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Epidermal growth factor receptor (EGFR) [4]

• Molecule Alteration: Complex-indel; p.E709_T710delinsD (c.2127_2129delAAC)
• 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: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Epidermal growth factor receptor (EGFR) [4]

• Molecule Alteration: Missense mutation; p.G719A (c.2156G>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: myelomonocyti cells; Bone marrow; Homo sapiens (Human); N.A.
• In Vitro Model: macrophage-like cells; N.A.; .; N.A.
• In Vitro Model: IL3-dependent murine pro-B cells; Blood; Homo sapiens (Human); N.A.
• In Vitro Model: Balb/C mouse leukemia cells; Blood; Mus musculus (Mouse); CVCL_9099
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Complex-indel; p.G776_776delinsVC (c.2326_2328delinsGTATGT)
• 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
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [3]

• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)/p.780_Y781insGSP
• 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
• Experiment for Molecule Alteration: Sanger cDNA sequencing assay
• Experiment for Drug Resistance: CCK-8 assay

Lung cancer [ICD-11: 2C25]

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: Duplication; p.N771_H773 (c.2311_2319)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

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

• Molecule Alteration: IF-insertion; p.P772_H773insPNP (c.2317_2318insCTAACCCTC)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: NSCLC cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; SDS-PAGE assay
• Experiment for Drug Resistance: MTS assay; Crystal violet staining assay
• Mechanism Description: Mutation in the covalent binding site of either EGFR or HER2 is sufficient to lead to drug resistance.

Key Molecule: Epidermal growth factor receptor (EGFR) [5]

• Molecule Alteration: Missense mutation; p.L858R (c.2573T>G)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [6]

• Molecule Alteration: Missense mutation; p.G719S (c.2155G>A)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [6]

• Molecule Alteration: Missense mutation; p.G719C (c.2155G>T)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [6]

• Molecule Alteration: Missense mutation; p.G719A (c.2156G>C)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data

Key Molecule: Epidermal growth factor receptor (EGFR) [7]

• Molecule Alteration: IF-deletion; p.G729_D761 (c.2185_2283)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [8]

• Molecule Alteration: Complex-indel; p.M774_774delinsWLV (c.2320_2322delinsTGGCTTGTA)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Clinical measurement assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [8]

• Molecule Alteration: Duplication; p.G778_P780 (c.2332_2340)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Clinical measurement assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [8]

• Molecule Alteration: IF-insertion; p.P780_Y781 (c.2340_2341)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Clinical measurement assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [8]

• Molecule Alteration: Complex-indel; p.M774delinsWLV (c.2320delinsTGGCTGG)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Clinical measurement assay

Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [8]

• Molecule Alteration: Duplication; p.P780_Y781 (c.2340_2341)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lung; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Clinical measurement assay

References

• Ref 1: Successful dacomitinib treatment after osimertinib resistance in a patient with lung adenocarcinoma .Clin Respir J. 2021 Jul;15(7):851-852. doi: 10.1111/crj.13360. Epub 2021 Mar 25. 10.1111/crj.13360
• Ref 2: Response Heterogeneity of EGFR and HER2 Exon 20 Insertions to Covalent EGFR and HER2 InhibitorsCancer Res. 2017 May 15;77(10):2712-2721. doi: 10.1158/0008-5472.CAN-16-3404. Epub 2017 Mar 31.
• Ref 3: Activity of a novel HER2 inhibitor, poziotinib, for HER2 exon 20 mutations in lung cancer and mechanism of acquired resistance: An in vitro studyLung Cancer. 2018 Dec;126:72-79. doi: 10.1016/j.lungcan.2018.10.019. Epub 2018 Oct 17.
• Ref 4: EGFR Exon 18 Mutations in Lung Cancer: Molecular Predictors of Augmented Sensitivity to Afatinib or Neratinib as Compared with First- or Third-Generation TKIsClin Cancer Res. 2015 Dec 1;21(23):5305-13. doi: 10.1158/1078-0432.CCR-15-1046. Epub 2015 Jul 23.
• Ref 5: Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutationsJ Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
• Ref 6: Management and future directions in non-small cell lung cancer with known activating mutationsAm Soc Clin Oncol Educ Book. 2014:e353-65. doi: 10.14694/EdBook_AM.2014.34.e353.
• Ref 7: Dacomitinib versus erlotinib in patients with EGFR-mutated advanced nonsmall-cell lung cancer (NSCLC): pooled subset analyses from two randomized trialsAnn Oncol. 2016 Mar;27(3):423-9. doi: 10.1093/annonc/mdv593. Epub 2016 Jan 13.
• Ref 8: Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumorsAnn Oncol. 2015 Jul;26(7):1421-7. doi: 10.1093/annonc/mdv186. Epub 2015 Apr 21.