Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H9Cl2F2N3OS |
Molecular Weight | 436.262 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CC=C(SC2=NN3C=NC(=O)C(=C3C=C2)C4=C(Cl)C=CC=C4Cl)C(F)=C1
InChI
InChIKey=VEPKQEUBKLEPRA-UHFFFAOYSA-N
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
VX-745 (Neflamapimod) is a brain-penetrant highly selective, orally bioavailable drug that inhibits the intracellular enzyme p38 mitogen-activated protein kinase alpha (MAPKa). It is currently in phase 2 clinical studies in patients with early Alzheimer's disease. The targeting of p38 MAPK by VX-745 was associated with the suppression of the release of inflammatory mediators, including interleukin (IL)-1β and tumor necrosis factor (TNF)α, known to be implicated in exacerbating the pathophysiology of rheumatoid arthritis (RA). The drug was in phase II of the clinical trial for RA, but that studies were discontinued.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2601 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900264 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
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OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
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Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [IC50 >10 uM] | ||||
no [IC50 >10 uM] | ||||
no [IC50 >40 uM] | ||||
no [IC50 >40 uM] | ||||
no [IC50 >40 uM] | ||||
no [IC50 >40 uM] | ||||
no [IC50 >40 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/24900264/ |
no | |||
yes [IC50 <10 uM] |
PubMed
Title | Date | PubMed |
---|---|---|
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT02423200
VX-745 dose level 1 twice daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11892915
Cell data for VX-745 in a human peripheral blood mononuclear cell (PBMC) assay provided IC50 values of 56 and 52 nM for IL-1β and TNFα, respectively, and VX-745 blocked IL-6 and IL-8 production induced by IL-1 and TNFα, and cyclooxygenase (COX)-2 synthesis mediated by LPS and IL-1β. In a human whole blood assay, IC50 values were 152 and 177 nM for IL-1β and TNFα inhibition, respectively.
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100000183677
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TYL52QM320
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10527
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3038525
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CD-175
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DB07138
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CHEMBL119385
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209410-46-8
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C170207
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DTXSID90175115
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ACTIVE MOIETY