Details of the Drug

General Information of Drug (ID: DMIHOYF)

Drug Name

GW-5074

Synonyms

gw5074; 220904-83-6; GW 5074; Raf1 Kinase Inhibitor I; UNII-B7W8RS1GG2; B7W8RS1GG2; CHEMBL72365; 5-Iodo-3-[(3,5-dibromo-4-hydroxyphenyl)methylene]-2-indolinone; 3-(3,5-Dibromo-4-hydroxy-benzylidene)-5-iodo-1,3-dihydro-indol-2-one; (3Z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one; (Z)-3-(3,5-Dibromo-4-hydroxybenzylidene)-5-iodoindolin-2-one; SR-01000075897; STO521; 3-(3,5-Dibromo-4-hydroxybenzyliden)-5-iodo-1,3-dihydroindol-2-one; Tocris-1381

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

520.94

Topological Polar Surface Area (xlogp)

4.6

Rotatable Bond Count (rotbonds)

1

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

2

Chemical Identifiers

Formula: C15H8Br2INO2
IUPAC Name: (3Z)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1H-indol-2-one
Canonical SMILES: C1=CC2=C(C=C1I)/C(=C/C3=CC(=C(C(=C3)Br)O)Br)/C(=O)N2
InChI: InChI=1S/C15H8Br2INO2/c16-11-4-7(5-12(17)14(11)20)3-10-9-6-8(18)1-2-13(9)19-15(10)21/h1-6,20H,(H,19,21)/b10-3-
InChIKey: LMXYVLFTZRPNRV-KMKOMSMNSA-N

Cross-matching ID

PubChem CID: 5924208
CAS Number: 1233748-60-1
TTD ID: D0Z5TQ

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Raf messenger RNA (Raf mRNA)	TTAN5W2	RAF1_HUMAN	Inhibitor	[2]
Tropomyosin-related kinase A (TrkA)	TTTDVOJ	NTRK1_HUMAN	Inhibitor	[2]

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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

Discovery agent

ICD Disease Classification

N.A.

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Tropomyosin-related kinase A (TrkA)	DTT	NTRK1	8.72E-01	-0.04	-0.22

Molecular Expression Atlas (MEA)

MEA Detail

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: 8072).
2	Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
4	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
5	Safety and efficacy of MIM-D3 ophthalmic solutions in a randomized, placebo-controlled Phase 2 clinical trial in patients with dry eye. Clin Ophthalmol. 2013; 7: 1275-1285.
6	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7	Topical TrkA Kinase Inhibitor CT327 is an Effective, Novel Therapy for the Treatment of Pruritus due to Psoriasis: Results from Experimental Studies, and Efficacy and Safety of CT327 in a Phase 2b Clinical Trial in Patients with Psoriasis. Acta Derm Venereol. 2015 May;95(5):542-8.
8	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9	Tropomyosin receptor kinase inhibitors: an updated patent review for 2010-2016 - Part I.Expert Opin Ther Pat. 2017 Jun;27(6):733-751.
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11	National Cancer Institute Drug Dictionary (drug id 766123).
12	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: 2184).
13	Clinical pipeline report, company report or official report of Roche.
14	Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
15	Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Anticancer Drugs. 2004 Mar;15(3):243-53.
16	Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J Med Chem. 2002 Jan 17;45(2):529-32.
17	The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
18	Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.