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)
Bioactivity Comments
In enzyme assays using PDE-4 isoforms the rank order of potency for CBS-3595 is D3 ∼D2 ≥ B1 ≥ A4 > C1 [1]. In a kinase profile screen several relevant off-targets were identified (JNK2α2, JNK3, and CK1δ may be relevant), although the MAPK δ and γ isoforms were not inhibited by CBS-3595 at a test concentration of 10 μM. CBS-3595 inhibits TNFα production in vitro with an IC50 of 700nM.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
mitogen-activated protein kinase 14 Hs Inhibitor Inhibition 6.3 pIC50 - 1
pIC50 6.3 (IC50 5x10-7 M) [1]
Description: In vitro determination.
phosphodiesterase 4D Hs Inhibitor Inhibition 6.1 pIC50 - 1
pIC50 6.1 (IC50 8x10-7 M) [1]
Description: Determined against the PDE4D3 splice variant.
phosphodiesterase 4B Hs Inhibitor Inhibition 5.7 pIC50 - 1
pIC50 5.7 (IC50 1.9x10-6 M) [1]
Description: Determined against the PDE4B1 splice variant.