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Compound Detail

CHEMBL5561973

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FC(F)c1c(Br)c(Br)cc2c1nc(N1CCNCC1)n2C1CCOCC1

Basic Information

ChEMBL ID CHEMBL5561973
Phase Preclinical
Structure Type MOL
InChI Key YRFOQHHFWYWAST-UHFFFAOYSA-N
24
Targets
29
Activities
1
Assay Types
24
PK Parameters
20
Publications
0
Known Names

Molecular Properties

494.2
MW (Da)
4.26
ALogP
5
HBA
1
HBD
42.3
PSA (Ų)
0.69
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C17H20Br2F2N4O
MW 494.18
Aromatic Rings 2
Heavy Atoms 26
NP-Likeness -0.94

Activity Summary

IC50 29 meas. best 8.68

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Cyclin-dependent kinase 8
CHEMBL5719
IC50 8.68 8.4 2.1 2
CDK8/Cyclin C
CHEMBL3038474
IC50 8.68 8.4 2.1 2
Cyclin-dependent kinase 19
CHEMBL6002
IC50 8.6 8.1 2.5 2
Dual specificity protein kinase CLK4
CHEMBL4203
IC50 8.54 8.54 2.9 1
MV4-11
CHEMBL613835
IC50 8.24 8.24 5.7 1
Dual specificity protein kinase CLK1
CHEMBL4224
IC50 8.09 8.09 8.2 1
Serine/threonine-protein kinase haspin
CHEMBL1075163
IC50 7.87 7.87 13.6 1
Dual specificity protein kinase CLK2
CHEMBL4225
IC50 7.84 7.84 14.3 1
Cyclin-dependent kinase 2/cyclin E1
CHEMBL1907605
IC50 7.5 7.5 31.4 1
MDA-MB-231
CHEMBL400
IC50 7.4 7.4 40.0 1
CDK2/Cyclin A2
CHEMBL3038469
IC50 7.37 7.37 42.6 1
Mitogen-activated protein kinase 15
CHEMBL5198
IC50 7.22 7.22 59.7 1
Casein kinase II subunit alpha'
CHEMBL4070
IC50 7.19 7.19 64.9 1
Cyclin-dependent kinase 5/CDK5 activator 1
CHEMBL1907600
IC50 7.06 6.885 87.4 2
Serine/threonine-protein kinase pim-2
CHEMBL4523
IC50 6.91 6.91 124.1 1
Casein kinase I isoform alpha
CHEMBL2793
IC50 6.88 6.88 132.3 1
Dual specificity tyrosine-phosphorylation-regulated kinase 1A
CHEMBL2292
IC50 6.8 6.8 158.0 1
CDK7/Cyclin H/MNAT1
CHEMBL3038473
IC50 6.71 6.71 197.0 1
Unchecked
CHEMBL612545
IC50 6.63 6.63 236.1 1
Rho-associated protein kinase 1
CHEMBL3231
IC50 6.45 6.45 353.0 1
Homeodomain-interacting protein kinase 3
CHEMBL4577
IC50 6.3 6.3 502.9 1
Cytochrome P450 1A2
CHEMBL3356
IC50 5.34 5.205 4580.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.24 5.24 5800.0 1
Serine/threonine-protein kinase TAO1
CHEMBL5261
IC50 5.17 5.17 6678.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 23883.0 ng.hr.mL-1 Mus musculus
AUC 1903.0 ng.hr.mL-1 Rattus norvegicus
AUC 5587.0 ng.hr.mL-1 Canis lupus familiaris
AUC 12515.0 ng.hr.mL-1 Macaca mulatta
CL 14.0 mL.min-1.kg-1 Mus musculus
CL 70.0 mL.min-1.kg-1 Rattus norvegicus
CL 12.0 mL.min-1.kg-1 Canis lupus familiaris
CL 13.0 mL.min-1.kg-1 Macaca mulatta
Cmax 2.276 ug.mL-1 Mus musculus
Cmax 0.1898 ug.mL-1 Rattus norvegicus
Cmax 0.475 ug.mL-1 Canis lupus familiaris
Cmax 1.098 ug.mL-1 Macaca mulatta
F 67.0 % Mus musculus
F 89.0 % Rattus norvegicus
F 85.0 % Canis lupus familiaris
F 218.0 % Macaca mulatta
T1/2 5.04 hr Mus musculus
T1/2 2.53 hr Rattus norvegicus
T1/2 4.75 hr Canis lupus familiaris
T1/2 7.0 hr Macaca mulatta
Tmax 1.5 hr Mus musculus
Tmax 2.0 hr Rattus norvegicus
Tmax 2.0 hr Canis lupus familiaris
Tmax 4.0 hr Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Cyclin-dependent kinase 8 IC50 = 2.08 nM 8.68 Inhibition of CDK8 (unknown origin) by HTRF assay 38690856
CDK8/Cyclin C IC50 = 2.1 nM 8.68 Displacement of tracer 236 from CDK8/cyclin C (unknown origin) preincubated for ... 38690856
Cyclin-dependent kinase 19 IC50 = 2.49 nM 8.6 Inhibition of CDK19 (unknown origin) by HTRF assay 38690856
Dual specificity protein kinase CLK4 IC50 = 2.9 nM 8.54 Inhibition of CLK4 (unknown origin) by ADP-Glo assay 38690856
MV4-11 IC50 = 5.7 nM 8.24 Antiproliferative activity against human MV4-11 cells incubated for 5 days by Ce... 38690856
CDK8/Cyclin C IC50 = 7.5 nM 8.12 Inhibition of CDK8/CyclinC (unknown origin) by ADP-Glo chemiluminescence assay 38690856
Cyclin-dependent kinase 8 IC50 = 7.5 nM 8.12 Inhibition of CDK8 (unknown origin) by ADP-Glo assay 38690856
Dual specificity protein kinase CLK1 IC50 = 8.2 nM 8.09 Inhibition of CLK1 (unknown origin) by ADP-Glo assay 38690856
Serine/threonine-protein kinase haspin IC50 = 13.6 nM 7.87 Inhibition of HASPIN (unknown origin) by ADP-Glo assay 38690856
Dual specificity protein kinase CLK2 IC50 = 14.3 nM 7.84 Inhibition of CLK2 (unknown origin) by ADP-Glo assay 38690856
Cyclin-dependent kinase 19 IC50 = 25.1 nM 7.6 Inhibition of CDK19 (unknown origin) by ADP-Glo assay 38690856
Cyclin-dependent kinase 2/cyclin E1 IC50 = 31.38 nM 7.5 Inhibition of CDK2/cyclinE1 (unknown origin) by ADP-Glo chemiluminescence assay 38690856
MDA-MB-231 IC50 = 40.0 nM 7.4 Inhibition of cell growth in human MDA-MB-231 cells 38690856
CDK2/Cyclin A2 IC50 = 42.62 nM 7.37 Inhibition of CDK2/cyclinA2 (unknown origin) by ADP-Glo chemiluminescence assay 38690856
Mitogen-activated protein kinase 15 IC50 = 59.7 nM 7.22 Inhibition of ERK8 (unknown origin) by ADP-Glo assay 38690856
Casein kinase II subunit alpha' IC50 = 64.9 nM 7.19 Inhibition of CSNK2A2 (unknown origin) by ADP-Glo assay 38690856
Cyclin-dependent kinase 5/CDK5 activator 1 IC50 = 87.43 nM 7.06 Inhibition of CDK5/p25NCK (unknown origin) by ADP-Glo chemiluminescence assay 38690856
Serine/threonine-protein kinase pim-2 IC50 = 124.1 nM 6.91 Inhibition of PIM2 (unknown origin) by ADP-Glo assay 38690856
Casein kinase I isoform alpha IC50 = 132.3 nM 6.88 Inhibition of CSNK1A1 (unknown origin) by ADP-Glo assay 38690856
Dual specificity tyrosine-phosphorylation-regulated kinase 1A IC50 = 158.0 nM 6.8 Inhibition of DYRK1A (unknown origin) by ADP-Glo assay 38690856

Literature References

PubMed DOI Target Context # Activities
38690856 10.1021/acs.jmedchem.4c00248 ADMET 35
38690856 10.1021/acs.jmedchem.4c00248 Unchecked 9
38690856 10.1021/acs.jmedchem.4c00248 MV4-11 5
38690856 10.1021/acs.jmedchem.4c00248 Cyclin-dependent kinase 5/CDK5 activator 1 4
38690856 10.1021/acs.jmedchem.4c00248 Cyclin-dependent kinase 8 3
38690856 10.1021/acs.jmedchem.4c00248 Cytochrome P450 1A2 2
38690856 10.1021/acs.jmedchem.4c00248 CDK8/Cyclin C 2
38690856 10.1021/acs.jmedchem.4c00248 MDA-MB-468 2
38690856 10.1021/acs.jmedchem.4c00248 CDK7/Cyclin H/MNAT1 2
38690856 10.1021/acs.jmedchem.4c00248 CDK2/Cyclin A2 2
38690856 10.1021/acs.jmedchem.4c00248 Cyclin-dependent kinase 2/cyclin E1 2
38690856 10.1021/acs.jmedchem.4c00248 Z-138 2
38690856 10.1021/acs.jmedchem.4c00248 Cyclin-dependent kinase 19 2
38690856 10.1021/acs.jmedchem.4c00248 CDK12/Cyclin K 1
38690856 10.1021/acs.jmedchem.4c00248 CDK18/Cyclin Y 1
38690856 10.1021/acs.jmedchem.4c00248 Cyclin-Y/Cyclin-dependent kinase 16 1
38690856 10.1021/acs.jmedchem.4c00248 CDK1/Cyclin E 1
38690856 10.1021/acs.jmedchem.4c00248 CDK9/cyclin T1 1
38690856 10.1021/acs.jmedchem.4c00248 CDK4/Cyclin D3 1
38690856 10.1021/acs.jmedchem.4c00248 CDK3/Cyclin E 1

Data from ChEMBL 36 via Core Engine