Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL4878072

Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
CN1CCN(C(=O)c2ccc3cc(CCNc4ccnc5ccc(C#N)cc45)ccc3c2)CC1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL4878072
Phase Preclinical
Structure Type MOL
InChI Key AFUHWZUYZJGVKM-UHFFFAOYSA-N
8
Targets
20
Activities
2
Assay Types
26
PK Parameters
10
Publications
0
Known Names

Molecular Properties

449.6
MW (Da)
4.30
ALogP
5
HBA
1
HBD
72.3
PSA (Ų)
0.49
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C28H27N5O
MW 449.56
Aromatic Rings 4
Heavy Atoms 34
NP-Likeness -1.36

Activity Summary

IC50 10 meas. best 8.44
Kd 10 meas. best 8.86

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
CDK8/Cyclin C
CHEMBL3038474
 Kd 8.86 8.86 1.4 1
Cyclin-C/Cyclin-dependent kinase 19
CHEMBL3883323
 Kd 8.54 8.54 2.9 1
CDK8/Cyclin C
CHEMBL3038474
 IC50 8.44 8.44 3.6 1
Cyclin-dependent kinase 8/19
CHEMBL3885556
 IC50 7.6 7.37 25.0 4
Cyclin-dependent kinase 19
CHEMBL6002
 Kd 7.36 7.36 44.0 2
Cyclin-dependent kinase 8
CHEMBL5719
 Kd 7.26 7.26 55.0 2
Unchecked
CHEMBL612545
 IC50 7.25 7.1033 56.0 3
Cyclin-dependent kinase 8
CHEMBL5719
 IC50 7.19 6.125 65.0 2
Mitogen-activated protein kinase kinase kinase kinase 2
CHEMBL5330
 Kd 6.03 6.03 940.0 2
Serine/threonine-protein kinase haspin
CHEMBL1075163
 Kd 6.0 6.0 1000.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 1573.33 ng.hr.mL-1 Mus musculus
AUC 817.0 ng.hr.mL-1 Mus musculus
AUC 6408.0 ng.hr.mL-1 Mus musculus
AUC 2182.0 ng.hr.mL-1 Mus musculus
AUC 331.0 ng.hr.mL-1 Mus musculus
AUC 88600.0 ng.hr.mL-1 Mus musculus
Cmax 2582.53 nM Mus musculus
Cmax 1085.51 nM Mus musculus
Cmax 320.31 nM Mus musculus
Cmax 12741.35 nM Mus musculus
F 73.0 % Mus musculus
F 16.5 % Mus musculus
F 34.6 % Mus musculus
MRT 0.2272 hr Homo sapiens
MRT 0.07083 hr Homo sapiens
T1/2 0.74 hr Mus musculus
T1/2 3.8 hr Mus musculus
T1/2 0.1575 hr Homo sapiens
T1/2 0.07083 hr Homo sapiens
T1/2 12.1 hr Mus musculus
T1/2 3.53 hr Mus musculus
T1/2 0.75 hr Mus musculus
T1/2 7.27 hr Mus musculus
Tmax 0.58 hr Mus musculus
Tmax 12.0 hr Mus musculus
Tmax 12.0 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
CDK8/Cyclin C Kd = 1.39 nM 8.86 Binding affinity to kinase tracer 236 binding to His tagged recombinant human CD... 35114084
Cyclin-C/Cyclin-dependent kinase 19 Kd = 2.9 nM 8.54 Binding affinity to recombinant human CDK19/cyclinC assessed as dissociation con... 35114084
CDK8/Cyclin C IC50 = 3.6 nM 8.44 Inhibition of kinase tracer 236 binding to His tagged recombinant human CDK8/cyc... 35114084
Cyclin-dependent kinase 8/19 IC50 = 25.0 nM 7.6 Inhibition of CDK8/CDK19 in TNF-alpha-induced HEK293 cells assessed as inhibitio... -
Cyclin-dependent kinase 8/19 IC50 = 35.0 nM 7.46 Inhibition of CDK8/CDK19 in TNF-alpha-induced HEK293 cells assessed as inhibitio... -
Cyclin-dependent kinase 8/19 IC50 = 36.0 nM 7.44 Inhibition of CDK8/CDK19 in TNF-alpha-induced HEK293 cells assessed as inhibitio... -
Cyclin-dependent kinase 19 Kd = 44.0 nM 7.36 Inhibition of human CDK19 by DiscoverX assay -
Cyclin-dependent kinase 19 Kd = 44.0 nM 7.36 Binding affinity to human CDK19 assessed as dissociation constant by KdELECT Dis... 35114084
Cyclin-dependent kinase 8 Kd = 55.0 nM 7.26 Inhibition of human CDK8 by DiscoverX assay -
Cyclin-dependent kinase 8 Kd = 55.0 nM 7.26 Binding affinity to human CDK8 assessed as dissociation constant by KdELECT Disc... 35114084
Unchecked IC50 = 56.0 nM 7.25 Inhibition of NF kappa B dependent CDK8/CDK19 in HEK293 cell incubated for 3 hrs... 35114084
Cyclin-dependent kinase 8 IC50 = 65.0 nM 7.19 Inhibition of CDK8 in TNF-alpha-induced HEK293 cells by NF-kappaB reporter assay -
Unchecked IC50 = 82.0 nM 7.09 Inhibition of prostate specific antigen (PSA) production in human LNCaP C4-2 cel... -
Cyclin-dependent kinase 8/19 IC50 = 105.0 nM 6.98 Inhibition of CDK8/CDK19 in HEK293 cells by NF-kappaB reporter assay -
Unchecked IC50 = 108.0 nM 6.97 Inhibition of CDK8/CDK19 in MV4-11 cells and measured after 7 days by Spectra ma... 35114084
Mitogen-activated protein kinase kinase kinase kinase 2 Kd = 940.0 nM 6.03 Inhibition of human MAP4K2 by DiscoverX assay -
Mitogen-activated protein kinase kinase kinase kinase 2 Kd = 940.0 nM 6.03 Binding affinity to human MAP4K2 assessed as dissociation constant by KdELECT Di... 35114084
Serine/threonine-protein kinase haspin Kd = 1000.0 nM 6.0 Inhibition of human HASPIN by DiscoverX assay -
Serine/threonine-protein kinase haspin Kd = 1000.0 nM 6.0 Binding affinity to human HASPIN assessed as dissociation constant by KdELECT Di... 35114084
Cyclin-dependent kinase 8 IC50 = 8765.0 nM 5.06 Inhibition of CDK8 in TNF-alpha-induced CDK8 and CDK19-knockout HEK293 cells by ... -

Literature References

PubMed DOI Target Context # Activities
35114084 10.1021/acs.jmedchem.1c01951 ADMET 25
35114084 10.1021/acs.jmedchem.1c01951 Unchecked 10
35114084 10.1021/acs.jmedchem.1c01951 CDK8/Cyclin C 6
35114084 10.1021/acs.jmedchem.1c01951 Cyclin-C/Cyclin-dependent kinase 19 5
35114084 10.1021/acs.jmedchem.1c01951 Cyclin-dependent kinase 8 2
35114084 10.1021/acs.jmedchem.1c01951 Cyclin-dependent kinase 19 2
35114084 10.1021/acs.jmedchem.1c01951 Serine/threonine-protein kinase haspin 2
35114084 10.1021/acs.jmedchem.1c01951 Mitogen-activated protein kinase kinase kinase kinase 2 2
35114084 10.1021/acs.jmedchem.1c01951 Myosin-IIIb 2
35114084 10.1021/acs.jmedchem.1c01951 MV4-11 1

Data from ChEMBL 36 via Core Engine