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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2D Structure
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Physico-chemical Properties
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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
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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
1. Alam J, Blackburn K, Patrick D. (2017)
Neflamapimod: Clinical Phase 2b-Ready Oral Small Molecule Inhibitor of p38α to Reverse Synaptic Dysfunction in Early Alzheimer's Disease.
J Prev Alzheimers Dis, 4 (4): 273-278. [PMID:29181493]
2. Alam JJ. (2015)
Selective Brain-Targeted Antagonism of p38 MAPKα Reduces Hippocampal IL-1β Levels and Improves Morris Water Maze Performance in Aged Rats.
J Alzheimers Dis, 48 (1): 219-27. [PMID:26401942]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
4. Duffy JP, Harrington EM, Salituro FG, Cochran JE, Green J, Gao H, Bemis GW, Evindar G, Galullo VP, Ford PJ et al.. (2011)
The Discovery of VX-745: A Novel and Selective p38α Kinase Inhibitor.
ACS Med Chem Lett, 2 (10): 758-63. [PMID:24900264]
5. Fitzgerald CE, Patel SB, Becker JW, Cameron PM, Zaller D, Pikounis VB, O'Keefe SJ, Scapin G. (2003)
Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity.
Nat Struct Biol, 10 (9): 764-9. [PMID:12897767]
6. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, Campbell BT, Chan KW, Ciceri P, Davis MI, Edeen PT et al.. (2008)
A quantitative analysis of kinase inhibitor selectivity.
Nat Biotechnol, 26 (1): 127-32. [PMID:18183025]
7. Munoz L, Ralay Ranaivo H, Roy SM, Hu W, Craft JM, McNamara LK, Chico LW, Van Eldik LJ, Watterson DM. (2007)
A novel p38 alpha MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model.
J Neuroinflammation, 4: 21. [PMID:17784957]
8. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]