doramapimod   

GtoPdb Ligand ID: 5668

Synonyms: BIRB 796BS | BIRB-796 | BIRB796
Compound class: Synthetic organic
Comment: Doramapimod is an allosteric p38 MAP kinase inhibitor [2-3].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 80.13
Molecular weight 527.29
XLogP 5.11
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Canonical SMILES O=C(Nc1cc(nn1c1ccc(cc1)C)C(C)(C)C)Nc1ccc(c2c1cccc2)OCCN1CCOCC1
Isomeric SMILES O=C(Nc1cc(nn1c1ccc(cc1)C)C(C)(C)C)Nc1ccc(c2c1cccc2)OCCN1CCOCC1
InChI InChI=1S/C31H37N5O3/c1-22-9-11-23(12-10-22)36-29(21-28(34-36)31(2,3)4)33-30(37)32-26-13-14-27(25-8-6-5-7-24(25)26)39-20-17-35-15-18-38-19-16-35/h5-14,21H,15-20H2,1-4H3,(H2,32,33,37)
InChI Key MVCOAUNKQVWQHZ-UHFFFAOYSA-N
No information available.
Summary of Clinical Use
Doramapimod (as research code BIRB 796) has been assessed in Phase II clinical trials for plaque-type psoriasis and rheumatoid arthritis (RA). Additional trials for RA and Crohn's disease were terminated. Development of the compound has not progressed beyond Phase II.
Mechanism Of Action and Pharmacodynamic Effects
p38 MAP kinases α and β are crucial in regulating the production of proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-1β. Doramapimod inhibits p38 MAP kinase activity, and has been shown to block TNFα release in LPS-stimulated THP-1 cells with an IC50 value of 18 nM [3].