CBS-3595   Click here for help

GtoPdb Ligand ID: 9610

Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: CBS-3595 is a dual inhibitor of p38α MAPK (MAPK14) and phosphodiesterase 4 (PDE-4) [1], a mechanism that represents a novel approach that may be useful for the treatment of pulmonary diseases (e.g. asthma and COPD) as well as other inflammatory diseases, for which there still exists a high level of unmet clinical need. The term Cytokine-Suppressive Anti-Inflammatory Drugs (CSAIDs) has been coined to describe compounds exploiting molecular mechanisms such as that targeted by CBS-3595.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 85.11
Molecular weight 356.11
XLogP 4.13
No. Lipinski's rules broken 0
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Canonical SMILES CSc1nc(c(n1C)c1ccnc(c1)NC(=O)C)c1ccc(cc1)F
Isomeric SMILES CSc1nc(c(n1C)c1ccnc(c1)NC(=O)C)c1ccc(cc1)F
InChI InChI=1S/C18H17FN4OS/c1-11(24)21-15-10-13(8-9-20-15)17-16(22-18(25-3)23(17)2)12-4-6-14(19)7-5-12/h4-10H,1-3H3,(H,20,21,24)
Immunopharmacology Comments
p38α MAPK and PDE-4 are two inflammation-related enzymes, suggesting potential benefit of dual inhibition in inflammatory conditions, especially those drive by TNFα. The dual inhibitor CBS-3595 is reported to attenuate inappropriate or excessive TNFα levels in relevant preclinical animal models [1]. This inhibitor functions at a level upstream of the actions of the anti-TNFα biologic therapies currently used in chronic inflammatory diseases, which rather than preventing TNFα biosynthesis or signalling, act to bind and neutralise freely circulating cytokine. In addition, small molecule therapies would help overcome some of the crucial limitations associated with the biological TNFα inhibitors (e.g. high level of non-responders, issues arising from their route of administration, and high costs).