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Compound Detail

CHEMBL3808884

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COC(=O)c1cc2cc(NCc3cc(NC(=O)c4cc(-n5cnc(C)c5)cc(C(F)(F)F)c4)ccc3C)cnc2[nH]1

Basic Information

ChEMBL ID CHEMBL3808884
Phase Preclinical
Structure Type MOL
InChI Key PGQWALGGBUYLQF-UHFFFAOYSA-N
20
Targets
28
Activities
2
Assay Types
7
PK Parameters
20
Publications
0
Known Names

Molecular Properties

562.5
MW (Da)
6.04
ALogP
7
HBA
3
HBD
113.9
PSA (Ų)
0.21
QED
2
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C29H25F3N6O3
MW 562.55
Aromatic Rings 5
Heavy Atoms 41
NP-Likeness -1.56

Activity Summary

IC50 15 meas. best 8.22
EC50 13 meas. best 10.4

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Bcr/Abl fusion protein
CHEMBL2096618
EC50 10.4 9.57 0.0 2
Tyrosine-protein kinase ABL1
CHEMBL1862
IC50 8.22 7.4975 6.0 4
Serine/threonine-protein kinase B-raf
CHEMBL5145
IC50 8.0 8.0 10.0 1
Epidermal growth factor receptor
CHEMBL203
IC50 7.82 7.385 15.0 2
NON-PROTEIN TARGET
CHEMBL3879801
EC50 7.66 7.2875 22.0 4
Tyrosine-protein kinase HCK
CHEMBL3234
IC50 7.66 7.66 22.0 1
HUVEC
CHEMBL613979
EC50 7.47 7.47 34.0 1
HT-29
CHEMBL384
EC50 7.43 7.43 37.0 1
Tyrosine-protein kinase Lyn
CHEMBL3905
IC50 7.43 7.43 37.0 1
HepG2
CHEMBL395
EC50 7.42 7.42 38.0 1
Proto-oncogene tyrosine-protein kinase Src
CHEMBL267
IC50 7.4 7.4 40.0 1
Tyrosine-protein kinase Yes
CHEMBL2073
IC50 7.36 7.36 44.0 1
Platelet-derived growth factor receptor alpha
CHEMBL2007
IC50 7.3 7.3 50.0 1
Tyrosine-protein kinase FRK
CHEMBL4223
IC50 7.21 7.21 62.0 1
A549
CHEMBL392
EC50 7.19 7.19 64.0 1
Tyrosine-protein kinase Lck
CHEMBL258
IC50 7.16 7.16 69.0 1
NCI-H1975
CHEMBL614348
EC50 6.98 6.98 104.0 1
Tyrosine-protein kinase Fyn
CHEMBL1841
IC50 6.88 6.88 131.0 1
MDA-MB-231
CHEMBL400
EC50 6.8 6.8 158.0 1
PBMC
CHEMBL613107
EC50 5.92 5.92 1200.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 558.0 ng.hr.mL-1 Mus musculus
AUC 3029.0 ng.hr.mL-1 Mus musculus
Cmax 1516.31 nM Mus musculus
Cmax 1084.35 nM Mus musculus
F 47.0 % Mus musculus
Tmax 0.167 hr Mus musculus
Tmax 0.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Bcr/Abl fusion protein EC50 = 0.04 nM 10.4 Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as ... 27010810
Bcr/Abl fusion protein EC50 = 1.8 nM 8.74 Inhibition of human BCR-ABL T315I mutant expressed in mouse BAF3 cells assessed ... 27010810
Tyrosine-protein kinase ABL1 IC50 = 6.0 nM 8.22 Inhibition of His-tagged full length human recombinant wild type ABL expressed i... 27010810
Serine/threonine-protein kinase B-raf IC50 = 10.0 nM 8.0 Inhibition of full length GST-tagged human recombinant BRAF V600E mutant express... 27010810
Epidermal growth factor receptor IC50 = 15.0 nM 7.82 Inhibition of GST-tagged human recombinant EGFR (668 to1210 residues) expressed ... 27010810
Tyrosine-protein kinase HCK IC50 = 22.0 nM 7.66 Inhibition of GST-tagged full length human recombinant HCK expressed in baculovi... 27010810
NON-PROTEIN TARGET EC50 = 22.0 nM 7.66 Antiproliferative activity against human Caki2 cells after 72 hrs by MTT assay 27010810
HUVEC EC50 = 34.0 nM 7.47 Antiangiogenic activity in HUVEC after 72 hrs by MTT assay 27010810
NON-PROTEIN TARGET EC50 = 35.0 nM 7.46 Antiproliferative activity against human BxPC3 cells after 72 hrs by MTT assay 27010810
HT-29 EC50 = 37.0 nM 7.43 Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay 27010810
Tyrosine-protein kinase Lyn IC50 = 37.0 nM 7.43 Inhibition of GST-tagged full length human recombinant LYNA expressed in baculov... 27010810
HepG2 EC50 = 38.0 nM 7.42 Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay 27010810
Proto-oncogene tyrosine-protein kinase Src IC50 = 40.0 nM 7.4 Inhibition of full length His-tagged human recombinant cSRC expressed in baculov... 27010810
Tyrosine-protein kinase Yes IC50 = 44.0 nM 7.36 Inhibition of GST-tagged full length human recombinant YES expressed in baculovi... 27010810
Tyrosine-protein kinase ABL1 IC50 = 46.0 nM 7.34 Inhibition of His-tagged full length human recombinant ABL G250E mutant expresse... 27010810
Platelet-derived growth factor receptor alpha IC50 = 50.0 nM 7.3 Inhibition of full length GST-tagged human recombinant PDGFRalpha expressed in b... 27010810
Tyrosine-protein kinase ABL1 IC50 = 51.0 nM 7.29 Inhibition of His-tagged full length human recombinant ABL Y253F mutant expresse... 27010810
NON-PROTEIN TARGET EC50 = 62.0 nM 7.21 Antiangiogenic activity in HRMEC after 72 hrs by MTT assay 27010810
Tyrosine-protein kinase FRK IC50 = 62.0 nM 7.21 Inhibition of GST-tagged full length human recombinant FRK expressed in baculovi... 27010810
A549 EC50 = 64.0 nM 7.19 Antiproliferative activity against human A549 cells after 72 hrs by MTT assay 27010810

Literature References

PubMed DOI Target Context # Activities
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase ABL1 9
27010810 10.1021/acs.jmedchem.6b00087 Mus musculus 7
27010810 10.1021/acs.jmedchem.6b00087 NON-PROTEIN TARGET 4
27010810 10.1021/acs.jmedchem.6b00087 Epidermal growth factor receptor 4
27010810 10.1021/acs.jmedchem.6b00087 Platelet-derived growth factor receptor alpha 3
27010810 10.1021/acs.jmedchem.6b00087 Serine/threonine-protein kinase B-raf 3
27010810 10.1021/acs.jmedchem.6b00087 Vascular endothelial growth factor receptor 1 2
27010810 10.1021/acs.jmedchem.6b00087 Proto-oncogene tyrosine-protein kinase Src 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase Fyn 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase HCK 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase Lyn 2
27010810 10.1021/acs.jmedchem.6b00087 Bcr/Abl fusion protein 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase Lck 2
27010810 10.1021/acs.jmedchem.6b00087 Vascular endothelial growth factor receptor 2 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase FRK 2
27010810 10.1021/acs.jmedchem.6b00087 Tyrosine-protein kinase Yes 2
27010810 10.1021/acs.jmedchem.6b00087 CDK2/Cyclin A2 1
27010810 10.1021/acs.jmedchem.6b00087 HepG2 1
27010810 10.1021/acs.jmedchem.6b00087 HT-29 1
27010810 10.1021/acs.jmedchem.6b00087 Cyclin-dependent kinase 1/cyclin B1 1

Data from ChEMBL 36 via Core Engine