General Information of Drug (ID: DMZIM37)

Drug Name
CP-868596
Synonyms
Crenolanib; 670220-88-9; Crenolanib (CP-868596); ARO-002; UNII-LQF7I567TQ; LQF7I567TQ; CP-868596 (Crenolanib); CP-868,596; [1-[2-[5-(3-Methyloxetan-3-ylmethoxy)benzimidazol-1-yl]quinolin-8-yl]piperidin-4-yl]amine; 1-(2-(5-((3-Methyloxetan-3-yl)methoxy)-1H-benzo-[d]imidazol-1-yl)quinolin-8-yl)piperidin-4-amine; CP868569; 1-[2-[5-[(3-Methyl-3-oxetanyl)methoxy]-1-benzimidazolyl]-8-quinolyl]-4-piperidinamine; J-502712; 1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine
Indication
Disease Entry ICD 11 Status REF
Gastrointestinal cancer 2C11 Phase 3 [1], [2]
Gastrointestinal stromal tumour 2B5B Phase 3 [3]
Acute myelogenous leukaemia 2A41 Phase 2 [4]
Acute myeloid leukaemia 2A60 Phase 2 [3]
Malignant glioma 2A00.0 Phase 1 [4]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 443.5
Topological Polar Surface Area (xlogp) 3.7
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C26H29N5O2
IUPAC Name
1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine
Canonical SMILES
CC1(COC1)COC2=CC3=C(C=C2)N(C=N3)C4=NC5=C(C=CC=C5N6CCC(CC6)N)C=C4
InChI
InChI=1S/C26H29N5O2/c1-26(14-32-15-26)16-33-20-6-7-22-21(13-20)28-17-31(22)24-8-5-18-3-2-4-23(25(18)29-24)30-11-9-19(27)10-12-30/h2-8,13,17,19H,9-12,14-16,27H2,1H3
InChIKey
DYNHJHQFHQTFTP-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
10366136
ChEBI ID
CHEBI:145365
CAS Number
670220-88-9
DrugBank ID
DB11832
TTD ID
D0J1GR

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Platelet-derived growth factor receptor alpha (PDGFRA) TT8FYO9 PGFRA_HUMAN Modulator [5], [6]
Proto-oncogene c-Src (SRC) TT6PKBN SRC_HUMAN Inhibitor [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Gastrointestinal cancer
ICD Disease Classification 2C11
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Platelet-derived growth factor receptor alpha (PDGFRA) DTT PDGFRA 3.46E-01 -0.23 -1.55
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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: 7882).
2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015430)
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 The FLT3 and PDGFR inhibitor crenolanib is a substrate of the multidrug resistance protein ABCB1 but does not inhibit transport function at pharmacologically relevant concentrations.Invest New Drugs.2015 Apr;33(2):300-9.
6 Crenolanib, a PDGFR inhibitor, suppresses lung cancer cell proliferation and inhibits tumor growth in vivo.Onco Targets Ther.2014 Sep 26;7:1761-8.
7 Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel... J Med Chem. 2003 Mar 27;46(7):1116-9.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
9 A phase I study of olaratumab, an anti-platelet-derived growth factor receptor alpha (PDGFRalpha) monoclonal antibody, in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Mar;73(3):595-604.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
11 E-3810 is a potent dual inhibitor of VEGFR and FGFR that exerts antitumor activity in multiple preclinical models. Cancer Res. 2011 Feb 15;71(4):1396-405.
12 Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
13 National Cancer Institute Drug Dictionary (drug id 452042).
14 Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol. 2014 Jul;74(1):195-204.
15 Clinical pipeline report, company report or official report of MedImmune (2011).
16 RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
17 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.
18 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.
19 In vivo antitumor activity of herbimycin A, a tyrosine kinase inhibitor, targeted against BCR/ABL oncoprotein in mice bearing BCR/ABL-transfected cells. Leuk Res. 1994 Nov;18(11):867-73.
20 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
21 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
22 Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
23 Clinical pipeline report, company report or official report of Turning Point Therapeutics.
24 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.