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)-
    Click to Show/Hide
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]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Lung cancer [ICD-11: 2C25]
[2]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[4]
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[3]
Target Epidermal growth factor receptor (EGFR) EGFR_HUMAN [1]
Erbb2 tyrosine kinase receptor (HER2) ERBB2_HUMAN [1]
Erbb4 tyrosine kinase receptor (Erbb-4) ERBB4_HUMAN [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
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 due to Structure Alteration
  ADTT: Aberration of the Drug's Therapeutic Target
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Lung cancer [ICD-11: 2C25]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [5]
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
 Disease Info 
Molecule Alteration Missense mutation
p.L858R (c.2573T>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 2.64  Å
PDB: 4LI5
Mutant Type Structure Method: X-ray diffraction Resolution: 2.47  Å
PDB: 2ITV
   Download The Information of Sequence       Download The Structure File   
RMSD: 1.34
TM score: 0.90001
Amino acid change:
L858R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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700
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710
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720
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730
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740
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750
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760
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770
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780
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790
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800
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810
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820
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830
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840
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850
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860
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870
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880
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890
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900
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910
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920
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930
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940
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950
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960
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970
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980
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990
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1000
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1010
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1020
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
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 PPP3CB overexpression mediates EGFR TKI resistance in lung tumors via calcineurin/MEK/ERK signaling. Life Sci Alliance. 2024 Oct 1;7(12):e202402873.
Ref 3 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 4 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 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.

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