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Compound Detail

CHEMBL459850

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Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1N1Cc2cnc(N)nc2N(C)C1=O

Basic Information

ChEMBL ID CHEMBL459850
Phase Preclinical
Structure Type MOL
InChI Key ZWVLMQTXUWMUII-UHFFFAOYSA-N
23
Targets
26
Activities
2
Assay Types
6
PK Parameters
20
Publications
0
Known Names

Molecular Properties

456.4
MW (Da)
4.21
ALogP
5
HBA
2
HBD
104.5
PSA (Ų)
0.61
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C22H19F3N6O2
MW 456.43
Aromatic Rings 3
Heavy Atoms 33
NP-Likeness -1.54

Activity Summary

EC50 16 meas. best 8.7
IC50 10 meas. best 9.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase Fes/Fps
CHEMBL5455
IC50 9.0 9.0 1.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 8.85 8.85 1.4 1
Ephrin type-A receptor 3
CHEMBL4954
EC50 8.7 8.7 2.0 1
Unchecked
CHEMBL612545
EC50 8.52 8.52 3.0 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
EC50 8.4 8.4 4.0 1
Platelet-derived growth factor receptor alpha
CHEMBL2007
EC50 8.4 8.4 4.0 1
Ephrin type-B receptor 4
CHEMBL5147
EC50 8.4 8.4 4.0 1
Tyrosine-protein kinase Lck
CHEMBL258
EC50 8.3 8.3 5.0 1
Platelet-derived growth factor receptor beta
CHEMBL1913
EC50 8.22 8.22 6.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
EC50 7.89 7.89 13.0 1
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 7.89 7.89 13.0 1
Activated CDC42 kinase 1
CHEMBL4599
IC50 7.75 7.75 18.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
EC50 7.66 7.66 22.0 1
Mitogen-activated protein kinase kinase kinase kinase 2
CHEMBL5330
IC50 7.55 7.55 28.0 1
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
EC50 7.52 7.52 30.0 1
NT-3 growth factor receptor
CHEMBL5608
EC50 7.52 7.52 30.0 1
Lysine--tRNA ligase
CHEMBL5575
EC50 7.15 7.15 71.0 1
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
EC50 7.11 7.11 77.0 1
Fibroblast growth factor receptor 1
CHEMBL3650
EC50 7.1 7.1 80.0 1
Angiopoietin-1 receptor
CHEMBL4128
EC50 6.7 6.7 200.0 1
Vascular endothelial growth factor receptor 1
CHEMBL1868
EC50 6.63 6.63 236.0 1
Tyrosine-protein kinase ABL1
CHEMBL3099
IC50 6.61 6.61 243.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.53 6.2667 294.0 3
Tyrosine-protein kinase ABL1
CHEMBL1862
IC50 5.8 5.8 1567.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 52464.8 ng.hr.mL-1 Mus musculus
AUC 36363.7 ng.hr.mL-1 Mus musculus
Cmax 5273.54 nM Mus musculus
MRT 18.1 hr Mus musculus
T1/2 12.4 hr Mus musculus
Tmax 2.7 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase Fes/Fps IC50 = 1.0 nM 9.0 Inhibition of Fes 18077425
Cytoplasmic tyrosine-protein kinase BMX IC50 = 1.4 nM 8.85 Inhibition of Bmx 18077425
Ephrin type-A receptor 3 EC50 = 2.0 nM 8.7 Inhibition of EphA3 by cellular assay 18077425
Unchecked EC50 = 3.0 nM 8.52 Inhibition of Bcr-abl by cellular assay 18077425
Platelet-derived growth factor receptor alpha EC50 = 4.0 nM 8.4 Inhibition of PDGFRalpha by cellular assay 18077425
Ephrin type-B receptor 4 EC50 = 4.0 nM 8.4 Inhibition of EphB4 by cellular assay 18077425
Mast/stem cell growth factor receptor Kit EC50 = 4.0 nM 8.4 Inhibition of c-Kit by cellular assay 18077425
Tyrosine-protein kinase Lck EC50 = 5.0 nM 8.3 Inhibition of Lck by cellular assay 18077425
Platelet-derived growth factor receptor beta EC50 = 6.0 nM 8.22 Inhibition of PDGFRbeta by cellular assay 18077425
Fibroblast growth factor receptor 3 IC50 = 13.0 nM 7.89 Inhibition of FGFR3 18077425
Proto-oncogene tyrosine-protein kinase Src EC50 = 13.0 nM 7.89 Inhibition of Src by cellular assay 18077425
Activated CDC42 kinase 1 IC50 = 18.0 nM 7.75 Inhibition of ACK1 (unknown origin) by radiometric biochemical kinase assay 30153003
Vascular endothelial growth factor receptor 2 EC50 = 22.0 nM 7.66 Inhibition of KDR by cellular assay 18077425
Mitogen-activated protein kinase kinase kinase kinase 2 IC50 = 28.0 nM 7.55 Inhibition of GCK (unknown origin) by radiometric biochemical kinase assay 30153003
NT-3 growth factor receptor EC50 = 30.0 nM 7.52 Inhibition of TrkC by cellular assay 18077425
Cytoplasmic tyrosine-protein kinase BMX EC50 = 30.0 nM 7.52 Inhibition of Bmx by cellular assay 18077425
Lysine--tRNA ligase EC50 = 71.0 nM 7.15 Inhibition of Syk by cellular assay 18077425
Proto-oncogene tyrosine-protein kinase receptor Ret EC50 = 77.0 nM 7.11 Inhibition of Ret by cellular assay 18077425
Fibroblast growth factor receptor 1 EC50 = 80.0 nM 7.1 Inhibition of FGFR1 by cellular assay 18077425
Angiopoietin-1 receptor EC50 = 200.0 nM 6.7 Inhibition of Tie2 by cellular assay 18077425

Literature References

PubMed DOI Target Context # Activities
18077425 10.1073/pnas.0707498104 NON-PROTEIN TARGET 112
30153003 10.1021/acs.jmedchem.8b00882 OCI-AML-3 14
20604564 10.1021/jm901808w NON-PROTEIN TARGET 10
30153003 10.1021/acs.jmedchem.8b00882 Activated CDC42 kinase 1 8
30153003 10.1021/acs.jmedchem.8b00882 BaF3 7
30153003 10.1021/acs.jmedchem.8b00882 Mus musculus 7
30153003 10.1021/acs.jmedchem.8b00882 Mitogen-activated protein kinase kinase kinase kinase 2 7
20604564 10.1021/jm901808w Tyrosine-protein kinase ABL1 6
18077425 10.1073/pnas.0707498104 COLO 4
30153003 10.1021/acs.jmedchem.8b00882 ADMET 4
18077425 10.1073/pnas.0707498104 Cytoplasmic tyrosine-protein kinase BMX 2
18077425 10.1073/pnas.0707498104 SK-MES-1 2
18077425 10.1073/pnas.0707498104 Fibroblast growth factor receptor 1 1
18077425 10.1073/pnas.0707498104 Mast/stem cell growth factor receptor Kit 1
18077425 10.1073/pnas.0707498104 Vascular endothelial growth factor receptor 2 1
18077425 10.1073/pnas.0707498104 Vascular endothelial growth factor receptor 1 1
18077425 10.1073/pnas.0707498104 Ephrin type-A receptor 3 1
18077425 10.1073/pnas.0707498104 Unchecked 1
18077425 10.1073/pnas.0707498104 Macrophage-stimulating protein receptor 1
30153003 10.1021/acs.jmedchem.8b00882 Ephrin type-A receptor 1 1

Data from ChEMBL 36 via Core Engine