Details of the Drug

General Information of Drug (ID: DMNFZOT)

Drug Name

TAK-593

Synonyms

TAK-593; 1005780-62-0; UNII-H3I42X8XX7; H3I42X8XX7; CHEMBL2180604; 1H-Pyrazole-5-carboxamide, N-[5-[[2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl]oxy]-2-methylphenyl]-1,3-dimethyl-;1H-Pyrazole-5-carboxamide, N-[5-[[2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl]oxy]-2-methylphenyl]-1,3-dimethyl-; TAK 593; SCHEMBL2515478; DZFZXPPHBWCXPQ-UHFFFAOYSA-N; ZINC95579919; BDBM50399537; AKOS030526192; CS-2403; DB13093; NCGC00485933-01; 1H-Pyrazole-5-carboxamide, N-(5-((2-((cyclopropylcarbonyl)amino)imidazo

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

445.5

Topological Polar Surface Area (xlogp)

2.4

Rotatable Bond Count (rotbonds)

6

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

6

Chemical Identifiers

Formula: C23H23N7O3
IUPAC Name: N-[5-[2-(cyclopropanecarbonylamino)imidazo[1,2-b]pyridazin-6-yl]oxy-2-methylphenyl]-2,5-dimethylpyrazole-3-carboxamide
Canonical SMILES: CC1=C(C=C(C=C1)OC2=NN3C=C(N=C3C=C2)NC(=O)C4CC4)NC(=O)C5=CC(=NN5C)C
InChI: InChI=1S/C23H23N7O3/c1-13-4-7-16(11-17(13)24-23(32)18-10-14(2)27-29(18)3)33-21-9-8-20-25-19(12-30(20)28-21)26-22(31)15-5-6-15/h4,7-12,15H,5-6H2,1-3H3,(H,24,32)(H,26,31)
InChIKey: DZFZXPPHBWCXPQ-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 24767976
CAS Number: 1005780-62-0
DrugBank ID: DB13093
TTD ID: D0T2ER

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-derived growth factor receptor beta (PDGFRB)	TTI7421	PGFRB_HUMAN	Modulator	[2], [1]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Modulator	[2], [1]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Vascular endothelial growth factor receptor 2 (KDR)	DTT	KDR	1.98E-01	0.11	0.2
Platelet-derived growth factor receptor beta (PDGFRB)	DTT	PDGFRB	5.35E-10	0.36	0.89

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Anti-angiogenic and anti-tumor effects of TAK-593, a potent and selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptor tyrosine kinase. Cancer Sci. 2013Apr;104(4):486-94.
2	Biochemical characterization of TAK-593, a novel VEGFR/PDGFR inhibitor with a two-step slow binding mechanism. Biochemistry. 2011 Feb 8;50(5):738-51.
3	Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
4	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.
5	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
6	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.
7	Metabolism and bioactivation of famitinib, a novel inhibitor of receptor tyrosine kinase, in cancer patients. Br J Pharmacol. 2013 Apr;168(7):1687-706.
8	National Cancer Institute Drug Dictionary (drug id 452042).
9	MK-2461, a novel multitargeted kinase inhibitor, preferentially inhibits the activated c-Met receptor. Cancer Res. 2010 Feb 15;70(4):1524-33.
10	Company report (Neuronova)
11	RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99.
12	Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
13	Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
14	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
15	2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
16	Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
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	Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
19	Clinical pipeline report, company report or official report of Exelixis (2011).
20	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
21	Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.