neflamapimod   Click here for help

GtoPdb Ligand ID: 5719

Synonyms: VD-31745 | VRT-031745 | VX 745 | VX-745
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Neflamapimod (VX-745) is an ATP-competitive inhibitor of mitogen-activated protein kinase p38α [4,6] that was originally assessed in preclinical investigations for antiarthritic/antiinflammatory activity. More recently the compound is being repurposed since the p38α mechanism may modulate Alzheimer's specific inflammatory processes [2].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

neflamapimod is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 3
Topological polar surface area 72.56
Molecular weight 434.98
XLogP 7.47
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Fc1ccc(c(c1)F)Sc1ccc2n(n1)cnc(=O)c2c1c(Cl)cccc1Cl
Isomeric SMILES Fc1ccc(c(c1)F)Sc1ccc2n(n1)cnc(=O)c2c1c(Cl)cccc1Cl
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
InChI Key VEPKQEUBKLEPRA-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
After in-licensing EIP Pharma began Phase 2 clinical trials for Alzheimer's disease in June 2015. These trials, NCT02423200 and NCT02423122, have now been completed (Dec 2017), with some positive results meriting progression to Phase 2b evaluation [1].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
VX-745 has been used to show that a glycine at position 110 is essential for the observed specificity of quinazolinone and pyridol-pyrimidine classes of p38 MAP kinase inhibitors [5]. This glycine is present in the α, β and γ isoforms but not in the δ isoform or other MAP kinases.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT02423122 A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD) Phase 2 Interventional EIP Pharma Inc
NCT02423200 Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD Phase 2 Interventional EIP Pharma Inc
NCT03435861 Effect of Neflamapimod on Brain Inflammation in Alzheimer's Disease Patients Phase 2 Interventional University Hospital, Toulouse