pamapimod   Click here for help

GtoPdb Ligand ID: 9915

Synonyms: compound 2b [PMID: 21375264] | Ro 4402257 | Ro-4402257 | Ro4402257
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Pamapimod is an ATP-competitive (Type I), orally bioavailable and highly selective inhibitor of p38α mitogen-activated protein kinase (MAPK14), that was developed for immunomodulatory potential [4].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 109.5
Molecular weight 406.15
XLogP 3.16
No. Lipinski's rules broken 0
Click here for help
Canonical SMILES OCCC(Nc1ncc2c(n1)n(C)c(=O)c(c2)Oc1ccc(cc1F)F)CCO
Isomeric SMILES OCCC(Nc1ncc2c(n1)n(C)c(=O)c(c2)Oc1ccc(cc1F)F)CCO
InChI InChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)
Immunopharmacology Comments
Pamapimod is a mitogen-activated protein kinase p38α/β (MAPK14/MAPK11) inhibitor that was developed for immunomodulatory potential [4]. Proof-of-concept of the clinical potential of p38 inhibition as an immunomodulatory modality in RA was published by Zhang et al. (2010) [6].
Immunopharmacology Disease
Disease X-Refs Comment References
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
Phase 2 clinical studies evaluating pamapimod (RO4402257) in RA patients either as a monotherapy (NCT00303563), or as an adjunct to methotrexate therapy (NCT00316771) have been completed. As a monotherapy pamapimod was not as effective as methotrexate, and in patients on a stable methotrexate regimen pamapimod showed no significant improvement in efficacy outcomes compared to placebo. 1