Details of the Drug

General Information of Drug (ID: DMIBUW5)

Drug Name

GW-788388

Synonyms

452342-67-5; GW788388; 4-(4-(3-(pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide; GW-788388; GW 788388; UNII-N14114957J; CHEMBL202887; N14114957J; 4-[4-[3-(Pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl]-N-(tetrahydropyran-4-yl)benzamide; N-(oxan-4-yl)-4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}benzamide; 4-(4-(3-(Pyridin-2-yl)-1H-pyrazol-4-yl)pyridin-2-yl)-N-(tetrahydropyran-4-yl)benzamide; cc-69; SCHEMBL373524; SCHEMBL17926774; CTK8C0589; DTXSID70196444; EX-A122; AOB2606

Indication

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

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

425.5

Topological Polar Surface Area (xlogp)

2.7

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C25H23N5O2
IUPAC Name: N-(oxan-4-yl)-4-[4-(5-pyridin-2-yl-1H-pyrazol-4-yl)pyridin-2-yl]benzamide
Canonical SMILES: C1COCCC1NC(=O)C2=CC=C(C=C2)C3=NC=CC(=C3)C4=C(NN=C4)C5=CC=CC=N5
InChI: InChI=1S/C25H23N5O2/c31-25(29-20-9-13-32-14-10-20)18-6-4-17(5-7-18)23-15-19(8-12-27-23)21-16-28-30-24(21)22-3-1-2-11-26-22/h1-8,11-12,15-16,20H,9-10,13-14H2,(H,28,30)(H,29,31)
InChIKey: SAGZIBJAQGBRQA-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 10202642
CAS Number: 452342-67-5
TTD ID: D0C3AD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
LCK tyrosine protein kinase (LCK)	TT860QF	LCK_HUMAN	Inhibitor	[1]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[1]
TGF-beta receptor type I (TGFBR1)	TTP4520	TGFR1_HUMAN	Inhibitor	[1]

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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

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
LCK tyrosine protein kinase (LCK)	DTT	LCK	4.46E-02	-0.13	-1.09

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Discovery of 4-{4-[3-(pyridin-2-yl)-1H-pyrazol-4-yl]pyridin-2-yl}-N-(tetrahydro-2H- pyran-4-yl)benzamide (GW788388): a potent, selective, and orall... J Med Chem. 2006 Apr 6;49(7):2210-21.
2	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.
3	National Cancer Institute Drug Dictionary (drug id 596693).
4	The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
5	Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
6	Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
7	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
8	Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitum... J Med Chem. 2005 Sep 8;48(18):5639-43.
9	Cardiac Safety of TGF-beta Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study. Cardiovasc Toxicol. 2015 Oct;15(4):309-23.
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11	Development of TGF-beta signalling inhibitors for cancer therapy. Nat Rev Drug Discov. 2004 Dec;3(12):1011-22.
12	Clinical pipeline report, company report or official report of Sumitomo Dainippon Pharma.
13	Novel potent inhibitor of Bcr-Abl mutated imatinib resistant chronic myeloid leukemia cell lines. Cancer Research. 06/2012; 72(8 Supplement):1822-1822.
14	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15	Targeting the TGF pathway for cancer therapy. Pharmacol Ther. 2015 Mar;147:22-31.
16	Pyrazolone based TGFbetaR1 kinase inhibitors. Bioorg Med Chem Lett. 2010 Jan 1;20(1):326-9.
17	TGF-beta type I receptor kinase inhibitor down-regulates rheumatoid synoviocytes and prevents the arthritis induced by type II collagen antibody. Int Immunol. 2007 Feb;19(2):117-26.
18	US patent application no. 2013,0028,978, Compositions and methods for wound treatment.
19	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
20	Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies. Arthritis Rheum. 2009 May;60(5):1232-41.
21	Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
22	c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.