CCT251921 |
CCT251921 : Inhibitor of CDK8, CDK19
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary
| Targets | Biochemical/Biophysical Potency | Cellular Potency |
|---|---|---|
| CDK8 |
|
|
| CDK19 |
|
Inhibitor
up to 1 uM
Selectivity
In Vitro Selectivity Assessment
Potency Assay Off-Target:
CCT-251921 was tested at 1 µM across a panel of 279
kinases (Millipore Panel: data expressed as perc ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
CCT-251921 was tested at 10 µM across a panel of 29 enzymes (CEREP) and tested at 10 µM across a pan ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
CCT-251921 was profiled for inhibitory activity in enzymatic activity assays covering 32 human CDK/c ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
CDK8, CDK19 and CDK8/19 Double Knockout Cells were used to assess the selectivity of compound CCT-25 ...
Potency Cellular
In Vitro
CDK8
Mode of Action: Inhibitor
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1021/acs.jmedchem.5b01685
CDK19
Mode of Action: Inhibitor
Structure-Activity-Relationship data available? Yes
DOI Reference: 10.1021/acs.jmedchem.5b01685
In Vivo Validations
Mouse
Dose: 0.2 mg/Kg IV, 0.5 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
0.78 h
Systemic clearance:
0.61 L/h/Kg
Bioavailability:
30%
Volume of Distribution at Steady-State:
0.63 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5b01685
Rat
Dose: 0.2 mg/Kg IV, 0.5 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
1.10 h
Systemic clearance:
1.49 L/h/Kg
Bioavailability:
57%
Volume of Distribution at Steady-State:
2.0 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5b01685
Dog
Dose: 0.2 mg/Kg IV, 0.5 mg/Kg PO
Route of delivery:
Intravenous, Oral
Plasma half life:
0.99 h
Systemic clearance:
1.07 L/h/Kg
Bioavailability:
68%
Volume of Distribution at Steady-State:
1.4 L/Kg
DOI Reference: 10.1021/acs.jmedchem.5b01685
Negative Control Compounds
canSAR3447722
Notes: CCT251099 is a structurally related but less active (20 fold) compound from the 3,4,5-trisubstituted series.
CCT252313
Notes: CT252313 lacks activity in multiple TCF/LEF reporter cell assays (IC₅₀ > 5 μM). CCT252313 did not demonstrate CDK8 binding into the micromolar range in competition bead binding assays but did retain some off-target binding activity.
SMILES:
O=C1NCCC12CN(C3=C(C4=CC=CC(N5CCN(CCC)CC5)=C4)C=NC=C3)CCC2
Chemical Information
| Molecular Formula | C21H23ClN6O |
| SMILEs | Cn1ncc2cc(-c3cnc(N)c(Cl)c3N3CCC4(CCNC4=O)CC3)ccc21 |
| InChI | InChI=1S/C21H23ClN6O/c1-27-16-3-2-13(10-14(16)11-26-27)15-12-25-19(23)17(22)18(15)28-8-5-21(6-9-28)4-7-24-20(21)29/h2-3,10-12H,4-9H2,1H3,(H2,23,25)(H,24,29) |
| Molecular weight | 410.16 Da |
| AlogP | 2.977400000000001 |
| HBond acceptors | 7 |
| HBond donors | 3 |
| Atoms | 52 |