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)
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Summary of Clinical Use Click here for help
Dose-limiting adverse events associated with inhibition of PDE-4 (nausea, vomiting and malaise, 1−2 h postdose) experienced by four first-in-human test subjects led to discontinuation of the clinical study of CBS-3595. This was determined to be due to high levels of active metabolite CBS-3728 (PubChem CID 11012474) in humans (less of this metabolite was measured in preclinical monkey studies) and this metabolite appeared to be selective for the PDE4D3 isoform, which is considered to be responsible for the nausea/vomiting side effects of PDE4 inhibitors. Therefore, isoform selectivity is an essential consideration for the development of future clinical candidates.