SS-208   Click here for help

GtoPdb Ligand ID: 10490

Synonyms: compound 7b [PMID: 31414801] | SS208
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: SS-208 is reported as an isotype selective inhibitor of histone deacetylase 6 (HDAC6) [2]. It has been developed for potential to treat advanced melanoma. SS-208 has been designed to provide improved HDAC6 selectivity compared to ricolinostat and citarinostat which both exhibit unfavourable levels of HDAC1 inhibition.
Selective pharmacological inhibition or genetic abrogation of HDAC6 modulates immune checkpoint activity by downregulating the expression of PD-L1 via the recruitment and activation of STAT3 [1]. The antitumour activity of SS-208 in vivo is primarily mediated by activation of immune cells and an anti-tumour immune response in the tumour microenvironment.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 104.46
Molecular weight 343.01
XLogP 2.16
No. Lipinski's rules broken 0
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Canonical SMILES ONC(=O)c1noc(c1)CCNC(=O)c1ccc(c(c1)Cl)Cl
Isomeric SMILES ONC(=O)c1noc(c1)CCNC(=O)c1ccc(c(c1)Cl)Cl
InChI InChI=1S/C13H11Cl2N3O4/c14-9-2-1-7(5-10(9)15)12(19)16-4-3-8-6-11(18-22-8)13(20)17-21/h1-2,5-6,21H,3-4H2,(H,16,19)(H,17,20)
Bioactivity Comments
We have included inhibitory constants for HDAC isozymes where the determined IC50 values were <10 μM.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
histone deacetylase 6 Primary target of this compound Hs Inhibitor Inhibition 7.9 pIC50 - 2
pIC50 7.9 (IC50 1.2x10-8 M) [2]
histone deacetylase 8 Hs Inhibitor Inhibition 5.9 pIC50 - 2
pIC50 5.9 (IC50 1.23x10-6 M) [2]
histone deacetylase 1 Hs Inhibitor Inhibition 5.9 pIC50 - 2
pIC50 5.9 (IC50 1.39x10-6 M) [2]
histone deacetylase 11 Hs Inhibitor Inhibition 5.3 pIC50 - 2
pIC50 5.3 (IC50 5.12x10-6 M) [2]
histone deacetylase 5 Hs Inhibitor Inhibition 5.2 pIC50 - 2
pIC50 5.2 (IC50 6.91x10-6 M) [2]
histone deacetylase 7 Hs Inhibitor Inhibition 5.1 pIC50 - 2
pIC50 5.1 (IC50 8.34x10-6 M) [2]