Details of the Drug

General Information of Drug (ID: DMSI8N3)

Drug Name

CI-1033

Synonyms

Canertinib; Canertinib HCl; Canertinib dihydrochloride; Canertinib dihydrochloride [USAN]; CI1033; PD 183805; Canertinib dihydrochloride (USAN); PD-0183805; PD-183805; Canertinib, PD-183805, CI1033, PD183805; N-[4-(3-Chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]acrylamide dihydrochloride; N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-2-propenamide dihydrochloride; N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide; 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-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; N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(3-(morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide; 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

Indication

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[1], [2]

Therapeutic Class

Anticancer Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

485.9

Topological Polar Surface Area (xlogp)

3.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

Chemical Identifiers

Formula: C24H25ClFN5O3
IUPAC Name: N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide
Canonical SMILES: C=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OCCCN4CCOCC4
InChI: InChI=1S/C24H25ClFN5O3/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)
InChIKey: OMZCMEYTWSXEPZ-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 156414
ChEBI ID: CHEBI:61399
CAS Number: 267243-28-7
DrugBank ID: DB05424
TTD ID: D0YB3W

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[3]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[3]
Erbb4 tyrosine kinase receptor (Erbb-4)	TT0JESD	ERBB4_HUMAN	Inhibitor	[3], [4]
RAC-alpha serine/threonine-protein kinase (AKT1)	TTWTSCV	AKT1_HUMAN	Inhibitor	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Lymphoma

ICD Disease Classification

2A80-2A86

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
RAC-alpha serine/threonine-protein kinase (AKT1)	DTT	AKT1	2.63E-29	0.65	1.45

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

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2	Tyrosine kinase inhibitors. 17. Irreversible inhibitors of the epidermal growth factor receptor: 4-(phenylamino)quinazoline- and 4-(phenylamino)pyrido[3,2-d]pyrimidine-6-acrylamides bearing additional solubilizing functions. J Med Chem. 2000 Apr 6;43(7):1380-97.
3	A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
4	A phase I clinical and pharmacokinetic study of oral CI-1033 in combination with docetaxel in patients with advanced solid tumors. Clin Cancer Res. 2006 Jul 15;12(14 Pt 1):4274-82.
5	Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
6	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7422).
7	Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
8	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
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11	Her2/neu is not a commonly expressed therapeutic target in melanoma -- a large cohort tissue microarray study. Melanoma Res. 2004 Jun;14(3):207-10.
12	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
13	Clinical pipeline report, company report or official report of Roche (2009).
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
15	Nasopharyngeal carcinoma: Current treatment options and future directions. J Nasopharyng Carcinoma, 2014, 1(16): e16.
16	Gefitinib ('Iressa', ZD1839) and new epidermal growth factor receptor inhibitors. Br J Cancer. 2004 Feb 9;90(3):566-72.
17	Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
18	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1797).
19	Synthesis and Src kinase inhibitory activity of a series of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-furyl-3-quinolinecarbonitriles. J Med Chem. 2006 Dec 28;49(26):7868-76.
20	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
21	Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64.
22	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
23	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1479).
24	CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
25	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1799).
26	A pilot study of JI-101, an inhibitor of VEGFR-2, PDGFR-, and EphB4 receptors, in combination with everolimus and as a single agent in an ovarian cancer expansion cohort.Invest New Drugs.2015 Dec;33(6):1217-24.
27	National Cancer Institute Drug Dictionary (drug id 596693).
28	Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity. J Med Chem. 2014 Jun 26;57(12):5112-28.
29	Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB... J Med Chem. 2006 Feb 23;49(4):1475-85.