compound 20 [Bergeron et al., 2016]   Click here for help

GtoPdb Ligand ID: 9171

PDB Ligand
Compound class: Synthetic organic
Comment: Compound 20 is a type II inhibitor (binds in a DMG-out mode) of CDK8, with an improved selectivity profile compared to sorafenib [2]. It is one of the compounds claimed in patent WO2015049325 [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 94.65
Molecular weight 479.23
XLogP 2.33
No. Lipinski's rules broken 0
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Canonical SMILES CNc1nccc(n1)N1CCC(C1)NC(=O)Nc1ccc(c(c1)C(F)(F)F)CN1CCOCC1
Isomeric SMILES CNc1nccc(n1)N1CC[C@@H](C1)NC(=O)Nc1ccc(c(c1)C(F)(F)F)CN1CCOCC1
InChI InChI=1S/C22H28F3N7O2/c1-26-20-27-6-4-19(30-20)32-7-5-17(14-32)29-21(33)28-16-3-2-15(18(12-16)22(23,24)25)13-31-8-10-34-11-9-31/h2-4,6,12,17H,5,7-11,13-14H2,1H3,(H,26,27,30)(H2,28,29,33)/t17-/m0/s1
Bioactivity Comments
At 1μM, compound 20 inhibits only 2 out of 220 kinases tested by >50% [2]. One of these hits is CDK8/cyclin C, the other is the receptor tyrosine kinase, fms related tyrosine kinase 3 (FLT3). However, it shows only weak anti-proliferative activity in cell assays, which is in concordance with results with other type II CDK8 inhibitors [3].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
cyclin dependent kinase 8 Primary target of this compound Hs Inhibitor Inhibition 7.8 pIC50 - 2
pIC50 7.8 (IC50 1.74x10-8 M) [2]