Drug General Information
Drug ID
D02NNV
Former ID
DCL000261
Drug Name
VX-745
Synonyms
VX745, VX-745; 5-(2,6-Dichlorophenyl)-2-((2,4-difluorophenyl)thio)-6H-pyrimido(1,6-b)pyridazin-6-one; 5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one
Drug Type
Small molecular drug
Indication Rheumatoid arthritis; Myelodysplastic syndrome [ICD9: 710-719, 714, 238.7; ICD10:M05-M06, D46] Phase 2 [525164], [541057], [544340]
Company
Vertex Pharma
Structure
Download
2D MOL

3D MOL

Formula
C19H9Cl2F2N3OS
InChI
InChI=1S/C19H9Cl2F2N3OS/c20-11-2-1-3-12(21)17(11)18-14-5-7-16(25-26(14)9-24-19(18)27)28-15-6-4-10(22)8-13(15)23/h1-9H
InChIKey
VEPKQEUBKLEPRA-UHFFFAOYSA-N
PubChem Compound ID
PubChem Substance ID
Target and Pathway
Target(s) MAP kinase p38 Target Info Inhibitor [536458], [536961]
KEGG Pathway MAPK signaling pathway
Rap1 signaling pathway
FoxO signaling pathway
Sphingolipid signaling pathway
Oocyte meiosis
Adrenergic signaling in cardiomyocytes
VEGF signaling pathway
Osteoclast differentiation
Signaling pathways regulating pluripotency of stem cells
Platelet activation
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
RIG-I-like receptor signaling pathway
T cell receptor signaling pathway
Fc epsilon RI signaling pathway
TNF signaling pathway
Leukocyte transendothelial migration
Neurotrophin signaling pathway
Retrograde endocannabinoid signaling
Dopaminergic synapse
Inflammatory mediator regulation of TRP channels
GnRH signaling pathway
Progesterone-mediated oocyte maturation
Prolactin signaling pathway
Amyotrophic lateral sclerosis (ALS)
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Salmonella infection
Pertussis
Leishmaniasis
Chagas disease (American trypanosomiasis)
Toxoplasmosis
Tuberculosis
Hepatitis C
Influenza A
Epstein-Barr virus infection
Proteoglycans in cancer
NetPath Pathway TCR Signaling Pathway
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
B cell activation
EGF receptor signaling pathway
FGF signaling pathway
Interferon-gamma signaling pathway
Oxidative stress response
Parkinson disease
TGF-beta signaling pathway
Ras Pathway
p53 pathway feedback loops 2
p38 MAPK pathway
Pathway Interaction Database RhoA signaling pathway
Signaling mediated by p38-gamma and p38-delta
Reactome NOD1/2 Signaling Pathway
p38MAPK events
Activation of PPARGC1A (PGC-1alpha) by phosphorylation
CDO in myogenesis
DSCAM interactions
VEGFA-VEGFR2 Pathway
WikiPathways Toll-like receptor signaling pathway
Insulin Signaling
MAPK Cascade
MAPK Signaling Pathway
Nanoparticle-mediated activation of receptor signaling
Signal Transduction of S1P Receptor
Parkinsons Disease Pathway
miR-targeted genes in muscle cell - TarBase
miR-targeted genes in lymphocytes - TarBase
NGF signalling via TRKA from the plasma membrane
Myogenesis
Integrin-mediated Cell Adhesion
DSCAM interactions
Regulation of toll-like receptor signaling pathway
References
Ref 525164ClinicalTrials.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.
Ref 541057(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).
Ref 544340Myelodysplastic Syndromes: Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2011 January; 9(1): 30-56.
Ref 536458Rapid synthesis of VX-745: p38 MAP kinase inhibition in Werner syndrome cells. Bioorg Med Chem Lett. 2007 Sep 15;17(18):5107-10. Epub 2007 Jul 13.
Ref 536961P38 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.

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