| 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 |
[1],
[2],
[3]
|
|---|
| 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 |
10049048, 14905671, 36106235, 46515551, 50100122, 50743824, 58670187, 85173223, 92719271, 93310134, 96022677, 99008617, 99437163, 99443609, 103344166, 103905630, 111646289, 118310938, 123051103, 124757265, 124950172, 125164069, 125344707, 126628288, 126651678, 126670738, 131305005, 131480883, 132048641, 134224254, 134338918, 134340669, 135141968, 136024966, 136340276, 136349964, 136367430, 136367729, 136378069, 140238366, 143497599, 152212967, 152239272, 152258175, 152344370, 160647012, 160812759, 160968223, 162011807, 162191904
|
| Target and Pathway |
| Target(s) |
MAP kinase p38 |
Target Info |
Inhibitor |
[4],
[5]
|
|---|
|
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 1 | 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. |
|---|
| REF 2 | (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 3 | Myelodysplastic Syndromes: Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2011 January; 9(1): 30-56. |
|---|
| REF 4 | Rapid 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 5 | 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. |
|---|
