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Cortistatin-A | Cortistatin-A : Inhibitor of CDK19, CDK8
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
CDK19
  • IC50:100 nM
  • IC 50:25-100 nM
CDK8
  • Kd:0.195 nM
  • IC 50:12 nM
  • IC50:10 nM
  • IC 50:25-100 nM
Inhibitor
1-1000 nM, 100 nM provides full inhibition of CDK8 and CDK19 in cells

Selectivity

In Vitro Selectivity Assessment

Potency: IC50

Potency Assay Off-Target:
In vitro kinase assay and Kinativ cell lysate displacement assay.
Selectivity Assessment Description:
No reproducible off-targets were validated up to 1 uM Cortistatin A. The only kinase affected in th ...

Potency
Cellular
In Vitro

CDK19

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nature14904

CDK8

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1038/nature14904

In Vivo Validations

Mouse
Dose: 1 mg/kg (PK study), 0.16 mg/kg once-daily (efficacy study)
Route of delivery: Intraperitoneal
Plasma half life: 12.7 hours (PK study)
Systemic clearance: 20 mL/min/kg (CL/F) (PK study)
Target engagement assay: Target engagement was indirectly determined by measuring a dose-dependent reduction in levels of STAT1-pS727 in natural killer cells.

DOI Reference: 10.1038/nature14904

Orthogonal Probes def

CCT251545

Chemical Information

Molecular Formula C30H36N2O3
SMILEs CN(C)[C@H]1C[C@@]23CC[C@@]4(O2)C(=CC[C@]2(C)[C@@H](c5ccc6ccncc6c5)CC[C@@H]42)C=C3[C@@H](O)[C@@H]1O
InChI InChI=1S/C30H36N2O3/c1-28-10-8-21-15-23-26(33)27(34)24(32(2)3)16-29(23)11-12-30(21,35-29)25(28)7-6-22(28)19-5-4-18-9-13-31-17-20(18)14-19/h4-5,8-9,13-15,17,22,24-27,33-34H,6-7,10-12,16H2,1-3H3/t22-,24+,25-,26-,27-,28-,29-,30-/m1/s1
Molecular weight 472.27 Da
AlogP 0.0
HBond acceptors 5
HBond donors 2
Atoms 71

References

Publications

Cross References

canSARChEMBLBindingDBPDB

Expert Reviews

by SERP
(on 24 Oct 2016 )
Cellular Use Rating
In Model Organisms
This is a potent and selective probe for CDK8 and its paralogue, CDK19. It was screened against a panel of 387 kinases (KiNativ) and shown to be completely selective for CDK8.
by SERP
(on 22 Dec 2016 )
Cellular Use Rating
In Model Organisms
The cortistatins are a group of steroidal alkaloids first isolated from the marine sponge Corticium simplex. Cortistatin A is a highly potent and selective inhibitor of CDK8 and CDK19, the kinases that...
Author’s note: Although Cortistatin A showed antiproliferative activity in HUVECs (IC50=1.8 nM) at a concentration below the Kd for Cortistatin A on CDK8 as reported in that publication (Angew Chem...
by SERP
(on 23 Jun 2017 )
Cellular Use Rating
Cortistatin A is a comprehensively characterized CDK8 inhibitor. Inhibitory activity was demonstrated in biochemical assays with three known substrates: CDK8 (autophosphorylation), STAT1-S727, and RNA...
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