Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMZIM37)

• Drug Name: CP-868596 Drug Info
• 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
• Cross-matching ID:
  PubChem CID: 10366136
  ChEBI ID: CHEBI:145365
  CAS Number: CAS 670220-88-9
  TTD Drug ID: DMZIM37

Molecule-Related Drug Atlas

Drug(s) Targeting Platelet-derived growth factor receptor alpha (PDGFRA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Romiplostim	DM3U7SZ	Thrombocytopenia	3B64	Approved	[7]
Ripretinib	DM958QB	Gastrointestinal stromal tumour	2B5B	Approved	[8]
Olaratumab	DMNYOIX	Soft tissue sarcoma	2B57	Approved	[9]
Avapritinib	DMK2GZX	Gastrointestinal stromal tumour	2B5B	Approved	[10]
E-3810	DM42PFT	Solid tumour/cancer	2A00-2F9Z	Phase 3	[11]
Famitinib	DMSFWT7	Solid tumour/cancer	2A00-2F9Z	Phase 2	[12]
XL-820	DMMHX9K	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
MP470	DMELUAK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[14]
MEDI-575	DMI9WVM	Glioblastoma multiforme	2A00.0	Phase 2	[15]
Pyridine derivative 18	DMBZMYT	N. A.	N. A.	Patented	[16]

Drug(s) Targeting Proto-oncogene c-Src (SRC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dasatinib	DMJV2EK	Chronic myelogenous leukaemia	2A20.0	Approved	[17]
Bosutinib	DMTI8YE	Breast cancer	2C60-2C65	Approved	[17]
SKI-758	DMQ8E9R	Ischemia	8B10-8B11	Approved	[18]
Herbimycin A	DM6YWBF	Solid tumour/cancer	2A00-2F9Z	Approved	[19]
Al3818	DM3WP0N	Alveolar soft part sarcoma	2A60-2C35	Phase 3	[3]
Masitinib	DMRSNEU	Amyotrophic lateral sclerosis	8B60.0	Phase 3	[20]
KX-01	DMF0NA9	Actinic keratosis	EK90.0	Phase 3	[21]
Saracatinib	DMBLHGP	Hematologic tumour	2B33.Y	Phase 2	[22]
TPX-0046	DMIVE67	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[23]
ISIS-CRP	DMQDUG4	Cardiovascular disease	BA00-BE2Z	Phase 1	[24]

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]

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.