Details of the Drug-Related molecule(s) Expression 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(s) Related to This Drug

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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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Stress-activated protein kinase 2a (p38 alpha)	DTT	MAPK14	7.103	6.87	6.74	6.306
Stress-activated protein kinase 2b (p38 beta)	DTT	MAPK11	3.907	2.485	3.655	2.945

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Alzheimer disease

ICD Disease Classification

8A20

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Stress-activated protein kinase 2a (p38 alpha)	DTT	MAPK14	4.95E-14	0.48	1.09
Stress-activated protein kinase 2b (p38 beta)	DTT	MAPK11	3.40E-03	-0.12	-0.29

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

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.