Drug Information

Drug (ID: DG80004) and It's Reported Resistant Information

• Name: Canertinib Dihydrochloride
• Synonyms: Canertinib dihydrochloride|289499-45-2|PD-0183805|PD-183805|CANERTINIB HYDROCHLORIDE|ICJ93X8X90|PD183805|PD-0183805-002B|DTXSID80183143|N-(4-(3-chloro-4-fluorophenyl)amino)-7-(3-morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide dihydrochloride|N-(4-((3-CHLORO-4-FLUOROPHENYL)AMINO)-7-(3-(4-MORPHOLINYL)PROPOXY)-6-QUINAZOLINYL)-2-PROPENAMIDE DIHYDROCHLORIDE|N-[4-(3-Chloro-4-fluorophenyl)amino]-7-(3-morpholin-4-yl)propoxy]quinazolin-6-yl]prop-2-enamide dihydrochloride|RefChem:202005|DTXCID90105634|663-691-3|N-(-4-((3-Chloro-4-fluorophenyl)amino)-7-(3-(4-morpholinyl)propoxy)-6-quinazolinyl)-2-propenamide Dihydrochloride|Canertinib HCl|CI-1033|Canertinib (dihydrochloride)|Canertinib dihydrochloride [USAN]|PD 183805|MFCD09954112|2-Propenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-, hydrochloride (1:2)|N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-morpholinopropoxy)quinazolin-6-yl)acrylamide dihydrochloride|N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide;dihydrochloride|Canertinib 2HCl|CI-1033 dihydrochloride;PD-183805 dihydrochloride|CHEMBL545315|Canertinib dihydrochloride (USAN)|N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(3-(morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide dihydrochloride|N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide dihydrochloride|SN-26606|UNII-ICJ93X8X90|Canertinib.2HCL|289499-45-2 (HCl)|Canertinib dihydrochloride?|C24H27Cl3FN5O3|Canertinib dihydrochloride salt|orb1305388|SCHEMBL2052123|SCHEMBL30436576|GLXC-05016|HMS3295E05|HY-10367A|AKOS015924656|AC-2414|CANERTINIB DIHYDROCHLORIDE [MI]|CS-0263|FC32740|2-Propenamide, N-(4-((3-chloro-4-fluorophenyl) amino)-7-(3-(4-morpholinyl) propoxy)-6-quinazolinyl)-, dihydrochloride|2-Propenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-morpholinyl)propoxy)-6-quinazolinyl)-, dihydrochloride|AS-75065|N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide dihydrochloride|N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide dihydrochloride|CANERTINIB DIHYDROCHLORIDE [WHO-DD]|S0711|CI-1033, >=98% (HPLC)|D03350|EN300-19659633|F862305|Q27280663|2-PROPENAMIDE, N-(4-((3-CHLORO-4-FLUOROPHENYL) AMINO)-7-(3-(4-MORPHOLINYL)PROPOXY)-6-QUINAZOLINYL)-, DIHYDROCHLORIDE|N-[4-(3-chloro-4-fluoro-anilino)-7-(3-morpholinopropoxy)quinazolin-6-yl]prop-2-enamide;dihydrochloride|N-[4-(3-Chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide dihydrochloride|N-{4-(3-Chloro-4-fluoroanilino)-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide--hydrogen chloride (1/2)
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Prostate cancer [ICD-11: 2C82]; [1]
• Formula: 9
• IsoSMILES: InChI=1S/C24H25ClFN5O3.2ClH/c1-2-23(32)30-21-13-17-20(14-22(21)34-9-3-6-31-7-10-33-11-8-31)27-15-28-24(17)29-16-4-5-19(26)18(25)12-16;;/h2,4-5,12-15H,1,3,6-11H2,(H,30,32)(H,27,28,29);2*1H
• InChI: C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4.Cl.Cl
• InChIKey: JZZFDCXSFTVOJY-UHFFFAOYSA-N
• PubChem CID: 156413

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

Prostate cancer [ICD-11: 2C82]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-203a [1]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DU145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR; Western blot; Luciferase Assay; Immunohistochemistry assay
• Experiment for Drug Resistance: Cell death and Proliferation Assay
• Mechanism Description: Here we show that ectopic miR-203 expression displayed reduced bone metastasis and induced sensitivity to tyrosine kinase inhibitors (TKIs) treatment in a xenograft model. Our results demonstrate that the induction of bone metastasis and TKI resistance require miR-203 down regulation, activation of the EGFR pathway via altered expression of EGFR ligands (EREG and TGFA) and anti-apoptotic proteins (API5, BIRC2, and TRIAP1). Importantly, a sufficient reconstitution of invasiveness and resistance to TKIs treatment was observed in cells transfected with anti-miR-203. In prostate cancer patients, our data showed that miR-203 levels were inversely correlated with the expression of two EGFR ligands, EREG and TGFA, and an EGFR dependent gene signature. Our results support the existence of a miR-203, EGFR, TKIs resistance regulatory network in prostate cancer progression. We propose that the loss of miR-203 is a molecular link in the progression of prostate cancer metastasis and TKIs resistance characterized by high EGFR ligands output and anti-apoptotic proteins activation.

References

• Ref 1: Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathwayMol Cancer Ther. 2014 May;13(5):1078-91. doi: 10.1158/1535-7163.MCT-13-0709. Epub 2014 Mar 14.