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Compound Detail

CHEMBL466397

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CCc1cc(Nc2nccc(-c3c(-c4ccc(OC)c(C(=O)Nc5c(F)cccc5F)c4)nc4ccccn34)n2)c(OC)cc1N1CCC(N2CCN(S(C)(=O)=O)CC2)CC1

Basic Information

ChEMBL ID CHEMBL466397
Phase Preclinical
Structure Type MOL
InChI Key MOSKATHMXWSZTQ-UHFFFAOYSA-N
45
Targets
153
Activities
2
Assay Types
9
PK Parameters
20
Publications
0
Known Names

Molecular Properties

852.0
MW (Da)
6.86
ALogP
12
HBA
2
HBD
146.5
PSA (Ų)
0.13
QED
3
Ro5 Violations
12
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C44H47F2N9O5S
MW 851.98
Aromatic Rings 6
Heavy Atoms 61
NP-Likeness -1.61

Activity Summary

IC50 149 meas. best 7.89
Ki 4 meas. best 8.89

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Insulin receptor
CHEMBL1981
Ki 8.89 8.89 1.3 2
Insulin-like growth factor 1 receptor
CHEMBL1957
Ki 8.8 8.8 1.6 2
Tyrosine-protein kinase Fer
CHEMBL3982
IC50 7.89 7.89 13.0 2
Tyrosine-protein kinase FRK
CHEMBL4223
IC50 7.8 7.8 16.0 2
Insulin receptor
CHEMBL1981
IC50 7.72 6.8388 19.0 32
Insulin-like growth factor 1 receptor
CHEMBL1957
IC50 7.66 6.8934 22.0 38
Unchecked
CHEMBL612545
IC50 7.46 6.92 35.0 5
NON-PROTEIN TARGET
CHEMBL3879801
IC50 7.46 7.2533 35.0 3
SK-N-MC
CHEMBL614163
IC50 7.37 7.37 43.0 1
PrEC
CHEMBL614239
IC50 7.17 7.17 68.0 1
NCI-H929
CHEMBL4296391
IC50 7.09 7.09 81.0 1
MOLP-8
CHEMBL5308502
IC50 7.02 7.02 96.0 1
Serine/threonine-protein kinase PAK 3
CHEMBL2999
IC50 6.99 6.99 103.0 2
LP-1
CHEMBL2366066
IC50 6.98 6.98 104.0 2
HT-29
CHEMBL384
IC50 6.98 6.98 104.0 1
KMS-12-BM
CHEMBL4296455
IC50 6.95 6.95 113.0 1
COLO 205
CHEMBL614561
IC50 6.91 6.91 124.0 2
MCF7
CHEMBL387
IC50 6.86 6.86 137.0 1
Tyrosine-protein kinase Fes/Fps
CHEMBL5455
IC50 6.83 6.83 148.0 2
Aurora kinase A
CHEMBL4722
IC50 6.8 6.8 159.0 2
Vascular endothelial growth factor receptor 3
CHEMBL1955
IC50 6.8 6.8 159.0 2
L-363
CHEMBL2366267
IC50 6.78 6.78 165.0 1
MX1
CHEMBL613704
IC50 6.72 6.72 189.0 1
Tyrosine-protein kinase HCK
CHEMBL3234
IC50 6.56 6.56 275.0 2
Tyrosine-protein kinase BTK
CHEMBL5251
IC50 6.45 6.45 357.0 1
Protein-tyrosine kinase 6
CHEMBL4601
IC50 6.45 6.45 357.0 1
Focal adhesion kinase 1
CHEMBL2695
IC50 6.44 6.44 362.0 2
Insulin receptor-related protein
CHEMBL5483
IC50 6.31 6.31 488.0 2
High affinity nerve growth factor receptor
CHEMBL2815
IC50 6.15 6.15 701.0 2
Cytoplasmic tyrosine-protein kinase BMX
CHEMBL3834
IC50 5.92 5.92 1214.0 2
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 5.73 5.73 1880.0 2
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
IC50 5.54 5.54 2850.0 2
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 5.5 5.5 3200.0 2
Tyrosine-protein kinase SYK
CHEMBL2599
IC50 5.5 5.5 3200.0 2
Inhibitor of nuclear factor kappa-B kinase subunit epsilon
CHEMBL3529
IC50 5.5 5.5 3200.0 1
Ribosomal protein S6 kinase alpha-4
CHEMBL3125
IC50 5.44 5.44 3640.0 2
Aurora kinase B
CHEMBL2185
IC50 5.4 5.3667 4000.0 3
PAS domain-containing serine/threonine-protein kinase
CHEMBL6054
IC50 5.36 5.36 4340.0 2
Tyrosine-protein kinase ABL1
CHEMBL1862
IC50 5.32 5.32 4749.0 2
Ribosomal protein S6 kinase alpha-1
CHEMBL2553
IC50 5.2 5.2 6300.0 2
Tyrosine-protein kinase Fyn
CHEMBL1841
IC50 5.2 5.2 6300.0 2
Tyrosine-protein kinase Lck
CHEMBL258
IC50 5.1 5.1 8000.0 2
Protein kinase C epsilon type
CHEMBL3582
IC50 5.0 5.0 10000.0 2
Mitogen-activated protein kinase 14
CHEMBL260
IC50 5.0 4.98 10000.0 2
Inhibitor of nuclear factor kappa-B kinase subunit alpha
CHEMBL3476
IC50 4.89 4.89 13000.0 2
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 4.89 4.89 13000.0 2
Inhibitor of nuclear factor kappa-B kinase subunit beta
CHEMBL1991
IC50 4.89 4.89 13000.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 1220.0 ng.hr.mL-1 Rattus norvegicus
AUC 870.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1070.0 ng.hr.mL-1 Macaca fascicularis
CL 5.8 mL.min-1.kg-1 Rattus norvegicus
CL 8.7 mL.min-1.kg-1 Canis lupus familiaris
CL 13.9 mL.min-1.kg-1 Macaca fascicularis
F 63.0 % Rattus norvegicus
F 47.0 % Canis lupus familiaris
F 97.0 % Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Insulin receptor Ki = 1.3 nM 8.89 Inhibition of intracellular domain of GST-tagged IR (979 to 1382 residues) (unkn... 19383820
Insulin receptor Ki = 1.3 nM 8.89 Binding affinity to insulin receptor by liquid scintillation counting 19101143
Insulin-like growth factor 1 receptor Ki = 1.6 nM 8.8 Inhibition of intracellular domain of GST-tagged IGF1R (957 to 1367 residues) (u... 19383820
Insulin-like growth factor 1 receptor Ki = 1.6 nM 8.8 Binding affinity to IGF1R by liquid scintillation counting 19101143
Tyrosine-protein kinase Fer IC50 = 13.0 nM 7.89 Inhibition of N-terminal His6 tagged recombinant human Fer (541 to end residues)... 19383820
Tyrosine-protein kinase Fer IC50 = 13.0 nM 7.89 Selectivity interaction (KinaseProfiler screening (Millipore, enzymatic assay)) ... -
Tyrosine-protein kinase FRK IC50 = 16.0 nM 7.8 Selectivity interaction (KinaseProfiler screening (Millipore, enzymatic assay)) ... -
Tyrosine-protein kinase FRK IC50 = 16.0 nM 7.8 Inhibition of N-terminal 6His-tagged recombinant human PTK5 (218 to end residues... 19383820
Insulin receptor IC50 = 19.0 nM 7.72 Inhibition of human IR autophosphorylation in insulin- stimulated mouse NIH-3T3-... 19383820
Insulin receptor IC50 = 19.0 nM 7.72 Inhibition of human insulin receptor autophosphorylation in transfected mouse NI... 19101143
Insulin receptor IC50 = 19.0 nM 7.72 Affinity On-target Cellular interaction: (Cellular mechanistic assay (measuring ... -
Insulin-like growth factor 1 receptor IC50 = 22.0 nM 7.66 Inhibition of human IGF1R autophosphorylation in transfected mouse NIH3T3 cells 19101143
Insulin-like growth factor 1 receptor IC50 = 22.0 nM 7.66 Affinity On-target Cellular interaction: (Cellular mechanistic assay (measuring ... -
Insulin-like growth factor 1 receptor IC50 = 22.0 nM 7.66 Inhibition of human IGF1R autophosphorylation in IGF1- stimulated mouse NIH-3T3/... 19383820
Insulin receptor IC50 = 25.0 nM 7.6 Affinity Biochemical interaction: (Enzymatic inhibition assay) EUB0000601a INSR -
Insulin receptor IC50 = 25.0 nM 7.6 Selectivity interaction (Enyzmatic assay) EUB0000601a INSR -
Insulin receptor IC50 = 25.0 nM 7.6 Inhibition of intracellular domain of GST-tagged IR (979 to 1382 residues) (unkn... 19383820
Insulin receptor IC50 = 25.0 nM 7.6 Selectivity interaction (Radiometric kinase assay (using 10 uM ATP)) EUB0000601a... -
Insulin receptor IC50 = 25.0 nM 7.6 Inhibition of GST-tagged insulin receptor expressed in baculovirus by time-resol... 19101143
Insulin-like growth factor 1 receptor IC50 = 27.0 nM 7.57 Inhibition of IGF1R (unknown origin) 33481605

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL5444388 Insulin-like growth factor 1 receptor 43
19383820 10.1158/1078-0432.ccr-08-2530 Unchecked 36
- 10.6019/CHEMBL5444388 Insulin receptor 36
19383820 10.1158/1078-0432.ccr-08-2530 Insulin receptor 24
19383820 10.1158/1078-0432.ccr-08-2530 Insulin-like growth factor 1 receptor 13
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
19383820 10.1158/1078-0432.ccr-08-2530 COLO 205 9
- 10.6019/CHEMBL4689842 Fibroblast 9
26254279 10.18632/oncotarget.4214 Insulin receptor 9
19383820 10.1158/1078-0432.ccr-08-2530 NCI-H929 8
- 10.6019/CHEMBL4689842 HEK-293T 8
19383820 10.1158/1078-0432.ccr-08-2530 MCF7 8
26254279 10.18632/oncotarget.4214 Insulin-like growth factor 1 receptor 8
- 10.6019/CHEMBL4689842 U2OS 8
19383820 10.1158/1078-0432.ccr-08-2530 ADMET 6
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
19383820 10.1158/1078-0432.ccr-08-2530 Proto-oncogene tyrosine-protein kinase Src 5
- 10.6019/CHEMBL5465560 Insulin-like growth factor 1 receptor 4
- 10.6019/CHEMBL5465560 Aurora kinase A 4

Data from ChEMBL 36 via Core Engine