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

General Information of Drug (ID: DMJAEG6)

Drug Name

VX-745 Drug Info

Synonyms

5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido[1,6-b]pyridazin-6-one; 209410-46-8; Neflamapimod; VX 745; VX745; VRT-031745; UNII-TYL52QM320; TYL52QM320; CHEBI:90528; 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenylthio)-6H-pyrimido[1,6-b]pyridazin-6-one; 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one; Neflamapimod (USAN); Neflamapimod [USAN]; AK-44905; C19H9Cl2F2N3OS; 5-(2,6-Dichlorophenyl)-2-[(2,4-Difluorophenyl)sulfanyl]-6h-Pyrimido[1,6-B]pyridazin-6-One; VX745, VX-745; 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido(1,6-b)pyridazin-6-one; Vertex 745 (VX745)

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[1] , [2]
Rheumatoid arthritis	FA20	Phase 2	[3] , [4] , [5]

Cross-matching ID

PubChem CID: 3038525
ChEBI ID: CHEBI:90528
CAS Number: CAS 209410-46-8
TTD Drug ID: DMJAEG6

Molecule-Related Drug Atlas

Molecule Type:

DTT

Drug Status:

Discontinued Drug(s)

Investigative Drug(s)

Approved Drug(s)

Clinical Trial Drug(s)

Patented Agent(s)

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Drug(s) Targeting Stress-activated protein kinase 2b (p38 beta)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[8]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[9]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[9]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[10]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[9]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[9]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[9]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[9]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[9]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[11]
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Drug(s) Targeting Stress-activated protein kinase 2a (p38 alpha)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ozagrel	DMIGKA1	Xerophthalmia	5B55.Y	Phase 4	[12]
Losmapimod	DMIL37Z	Acute coronary syndrome	BA41	Phase 3	[12]
VX-702	DMKJDR6	Coronary artery disease	BA80	Phase 2a	[13]
Dilmapimod	DMBYJ92	Acute lung injury	NB32.3	Phase 2	[12]
PMID25991433-Compound-A1	DM89LF0	N. A.	N. A.	Patented	[14]
PMID25991433-Compound-F2	DM37VIQ	N. A.	N. A.	Patented	[14]
PMID25991433-Compound-L2	DM58UO9	N. A.	N. A.	Patented	[14]
PMID25991433-Compound-L3	DM3LWUR	N. A.	N. A.	Patented	[14]
PMID25991433-Compound-L1	DM2135Y	N. A.	N. A.	Patented	[14]
PMID25991433-Compound-O2	DMTROIQ	N. A.	N. A.	Patented	[14]
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Drug(s) Targeting MAP kinase p38 (MAPK12)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SM-101	DMFX9O6	Idiopathic thrombocytopenic purpura	3B64.10	Approved (orphan drug)	[15]
ARRY-797	DMJ48AB	Dilated cardiomyopathy	BC43.0	Phase 2	[16]
KC706	DMBX6C7	Cardiovascular disease	BA00-BE2Z	Discontinued in Phase 2	[17]
SB 235699	DMNH8XU	Psoriasis vulgaris	EA90	Discontinued in Phase 1	[18]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[9]
Bisindolylmaleimide-I	DMOQJZC	Discovery agent	N.A.	Investigative	[9]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[10]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[9]
AMP-PNP	DMTOK1D	Discovery agent	N.A.	Investigative	[19]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[9]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
MAP kinase p38 (MAPK12)	TTYT93M	MK12_HUMAN	Inhibitor	[6] , [7]
Stress-activated protein kinase 2a (p38 alpha)	TTQBR95	MK14_HUMAN	Inhibitor	[8] , [1] , [2]
Stress-activated protein kinase 2b (p38 beta)	TT73U6C	MK11_HUMAN	Inhibitor	[8]

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References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3	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: 5719).
4	ClinicalTrials.gov (NCT02423200) Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD. U.S. National Institutes of Health.
5	Myelodysplastic Syndromes: Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2011 January; 9(1): 30-56.
6	P38 MAP kinase inhibitors as potential therapeutics for the treatment of joint degeneration and pain associated with osteoarthritis. J Inflamm (Lond). 2008 Dec 4;5:22.
7	Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10.
8	Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.
9	Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
10	Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47.
11	The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
12	Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
13	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.
14	c-Jun N-terminal kinase inhibitors: a patent review (2010 - 2014).Expert Opin Ther Pat. 2015;25(8):849-72.
15	Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
16	Array BioPharmas ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
17	KC706, an Oral p38 MAP Kinase Inhibitor, Increases HDL-C. Circulation. 2007;116:II_126.
18	Synthesis and structure-activity relationship of aminobenzophenones. A novel class of p38 MAP kinase inhibitors with high antiinflammatory activity. J Med Chem. 2003 Dec 18;46(26):5651-62.
19	The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.