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Compound Detail

CHEMBL4754081

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CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4)c(F)cn2)C1

Basic Information

ChEMBL ID CHEMBL4754081
Phase Preclinical
Structure Type MOL
InChI Key JTIFUJUJDWUQEV-LSDHHAIUSA-N
10
Targets
15
Activities
3
Assay Types
9
PK Parameters
19
Publications
0
Known Names

Molecular Properties

413.5
MW (Da)
3.30
ALogP
5
HBA
2
HBD
88.9
PSA (Ų)
0.80
QED
0
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C22H28FN5O2
MW 413.50
Aromatic Rings 2
Heavy Atoms 30
NP-Likeness -0.98

Activity Summary

IC50 13 meas. best 8.4
EC50 1 meas. best 7.54
Kd 1 meas. best 9.91

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
CDK9/cyclin T1
CHEMBL2111389
Kd 9.91 9.91 0.1 1
CDK9/cyclin T1
CHEMBL2111389
IC50 8.4 8.4 4.0 1
Cyclin-dependent kinase 9
CHEMBL3116
IC50 8.4 7.305 4.0 4
Cyclin-dependent kinase 3
CHEMBL4442
IC50 7.7 7.7 20.0 1
Cyclin-dependent kinase 9
CHEMBL3116
EC50 7.54 7.54 29.0 1
Cyclin-dependent kinase 2/cyclin E1
CHEMBL1907605
IC50 7.18 7.18 66.0 1
Cyclin-dependent kinase 1/cyclin B1
CHEMBL1907602
IC50 7.02 7.02 95.0 1
Cyclin-dependent kinase 4
CHEMBL331
IC50 6.48 6.48 334.0 1
Cyclin-dependent kinase 6
CHEMBL2508
IC50 6.27 6.27 532.0 1
CDK7/Cyclin H/MNAT1
CHEMBL3038473
IC50 6.26 6.26 548.0 1
Cyclin-dependent kinase 5
CHEMBL4036
IC50 5.56 5.56 2780.0 1
CDK12/Cyclin K
CHEMBL4106169
IC50 5.01 5.01 9850.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 53.0 mL.min-1.kg-1 Canis lupus familiaris
CL 70.0 mL.min-1.kg-1 Mus musculus
CL 19.0 mL.min-1.g-1 Homo sapiens
CL 104.0 mL.min-1.kg-1 Rattus norvegicus
Ka 4.62 /uM/s Homo sapiens
T1/2 0.43 hr Canis lupus familiaris
T1/2 0.16 hr Mus musculus
T1/2 0.18 hr Rattus norvegicus
T1/2 0.3383 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
CDK9/cyclin T1 Kd = 0.123 nM 9.91 Binding affinity to human CDK9/CyclinT assessed as equilibrium dissociation cons... 33306391
CDK9/cyclin T1 IC50 = 4.0 nM 8.4 Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 ... 33306391
Cyclin-dependent kinase 9 IC50 = 4.0 nM 8.4 Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro ... -
Cyclin-dependent kinase 3 IC50 = 20.0 nM 7.7 Inhibition of CDK3 (unknown origin) in presence of 5 mM ATP 33306391
Cyclin-dependent kinase 9 IC50 = 25.0 nM 7.6 Inhibition of CDK9 in human MCF7 cells assessed as reduction in RNA Polymerase 2... 33306391
Cyclin-dependent kinase 9 IC50 = 28.0 nM 7.55 Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro... -
Cyclin-dependent kinase 9 EC50 = 29.0 nM 7.54 Inhibition of CDK9 in human MV4-11 cells assessed as induction of caspase-3/7 ac... 33306391
Cyclin-dependent kinase 2/cyclin E1 IC50 = 66.0 nM 7.18 Inhibition of recombinant full length human CDK2/CyclinE expressed in insect cel... 33306391
Cyclin-dependent kinase 1/cyclin B1 IC50 = 95.0 nM 7.02 Inhibition of recombinant full length human His-tagged CDK1/CyclinB expressed in... 33306391
Cyclin-dependent kinase 4 IC50 = 334.0 nM 6.48 Inhibition of CDK4 (unknown origin) in presence of 5 mM ATP 33306391
Cyclin-dependent kinase 6 IC50 = 532.0 nM 6.27 Inhibition of CDK6 (unknown origin) in presence of 5 mM ATP 33306391
CDK7/Cyclin H/MNAT1 IC50 = 548.0 nM 6.26 Inhibition of recombinant full length human CDK7/cyclinH1/MAT1 expressed in inse... 33306391
Cyclin-dependent kinase 9 IC50 = 2134.0 nM 5.67 Kinase Assay (High ATP Concentration): Activity of CDK9 was determined in-vitro ... -
Cyclin-dependent kinase 5 IC50 = 2780.0 nM 5.56 Inhibition of CDK5 (unknown origin) in presence of 5 mM ATP 33306391
CDK12/Cyclin K IC50 = 9850.0 nM 5.01 Inhibition of human recombinant N-terminal GST-TEV tagged CDK12 (696 to 1082 res... 33306391

Literature References

PubMed DOI Target Context # Activities
33306391 10.1021/acs.jmedchem.0c01754 ADMET 20
33306391 10.1021/acs.jmedchem.0c01754 Unchecked 8
33306391 10.1021/acs.jmedchem.0c01754 CDK9/cyclin T1 6
33306391 10.1021/acs.jmedchem.0c01754 No relevant target 4
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 9 3
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 1/cyclin B1 2
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 2/cyclin E1 1
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 3 1
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 4 1
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 5 1
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 6 1
33306391 10.1021/acs.jmedchem.0c01754 CDK7/Cyclin H/MNAT1 1
33306391 10.1021/acs.jmedchem.0c01754 CDK12/Cyclin K 1
33306391 10.1021/acs.jmedchem.0c01754 Glycogen synthase kinase-3 alpha 1
33306391 10.1021/acs.jmedchem.0c01754 Glycogen synthase kinase-3 beta 1
33306391 10.1021/acs.jmedchem.0c01754 CDK2/Cyclin A2 1
33306391 10.1021/acs.jmedchem.0c01754 Cyclin-dependent kinase 7/ cyclin H 1
33306391 10.1021/acs.jmedchem.0c01754 Casein kinase I isoform gamma-1 1
33306391 10.1021/acs.jmedchem.0c01754 Dual specificity tyrosine-phosphorylation-regulated kinase 2 1

Data from ChEMBL 36 via Core Engine