Details of the Drug

General Information of Drug (ID: DMJKFNU)

Drug Name

DCC-2036

Synonyms

REBASTINIB; DCC-2036; 1020172-07-9; DCC-2036 (Rebastinib); DCC 2036; CHEBI:62166; UNII-75017Q6I97; Rebastinib(DCC-2036); 4-(4-(3-(3-(tert-butyl)-1-(quinolin-6-yl)-1H-pyrazol-5-yl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; DCC2036; DP-1919; 4-[4-({[3-Tert-Butyl-1-(Quinolin-6-Yl)-1h-Pyrazol-5-Yl]carbamoyl}amino)-3-Fluorophenoxy]-N-Methylpyridine-2-Carboxamide; 75017Q6I97; 4-[4-[(5-Tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide,4-methylbenzenesulfonic acid;4-[4-[(

Indication

Disease Entry	ICD 11	Status	REF
Chronic myeloid leukaemia	2A20	Phase 1/2	[1]
Acute lymphoblastic leukaemia	2A85	Phase 1	[1]
Breast cancer	2C60-2C65	Phase 1	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

553.6

Topological Polar Surface Area (xlogp)

4.9

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

7

Chemical Identifiers

Formula: C30H28FN7O3
IUPAC Name: 4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide
Canonical SMILES: CC(C)(C)C1=NN(C(=C1)NC(=O)NC2=C(C=C(C=C2)OC3=CC(=NC=C3)C(=O)NC)F)C4=CC5=C(C=C4)N=CC=C5
InChI: InChI=1S/C30H28FN7O3/c1-30(2,3)26-17-27(38(37-26)19-7-9-23-18(14-19)6-5-12-33-23)36-29(40)35-24-10-8-20(15-22(24)31)41-21-11-13-34-25(16-21)28(39)32-4/h5-17H,1-4H3,(H,32,39)(H2,35,36,40)
InChIKey: WVXNSAVVKYZVOE-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 25066467
ChEBI ID: CHEBI:62166
CAS Number: 1020172-07-9
DrugBank ID: DB13005
TTD ID: D0E0NM

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Angiopoietin 1 receptor (TEK)	TT9VGXW	TIE2_HUMAN	Inhibitor	[2]
Tyrosine-protein kinase ABL1 (ABL)	TT3PJMV	ABL1_HUMAN	Modulator	[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

Chronic myeloid leukaemia

ICD Disease Classification

2A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tyrosine-protein kinase ABL1 (ABL)	DTT	ABL1	2.14E-05	-0.34	-0.82

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT00827138) Study Safety and Preliminary Efficacy of DCC-2036 in Patients With Leukemias (Ph+ CML With T315I Mutation). U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	Company report (Deciphera Pharmaceuticals: Tumor-Targeted Programs and Indications)
4	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5	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.
6	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.
7	Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm. 2007 Dec 15;64(24 Suppl 15):S9-15.
8	Novel dual Src/Abl inhibitors for hematologic and solid malignancies.Expert Opin Investig Drugs.2010 Aug;19(8):931-45.
9	Flumatinib, a selective inhibitor of BCR-ABL/PDGFR/KIT, effectively overcomes drug resistance of certain KIT mutants. Cancer Sci. 2014 Jan;105(1):117-25.
10	Structure-based optimization of pyrazolo[3,4-d]pyrimidines as Abl inhibitors and antiproliferative agents toward human leukemia cell lines. J Med Chem. 2008 Mar 13;51(5):1252-9.
11	KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.
12	Inhibitors of JAK-family kinases: an update on the patent literature 2013-2015, part 1.Expert Opin Ther Pat. 2017 Feb;27(2):127-143.
13	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14	Clinical pipeline report, company report or official report of Deciphera Pharmaceuticals.
15	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: 1842).
16	Cmpany report (Arraybiopharma)
17	Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81.
18	Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8.
19	Pyrrolo[2,3-d]pyrimidines containing an extended 5-substituent as potent and selective inhibitors of lck I. Bioorg Med Chem Lett. 2000 Oct 2;10(19):2167-70.