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Compound Detail

CHEMBL5595500

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C[C@@H](Oc1ccc2[nH]nc(-c3ccc(N4CC5(C4)CN(S(C)(=O)=O)C5)nc3)c2c1)c1c(Cl)cncc1Cl

Basic Information

ChEMBL ID CHEMBL5595500
Phase Preclinical
Structure Type MOL
InChI Key JOAFWIHZEBKYQK-OAHLLOKOSA-N
16
Targets
29
Activities
1
Assay Types
30
PK Parameters
17
Publications
0
Known Names

Molecular Properties

559.5
MW (Da)
4.55
ALogP
7
HBA
1
HBD
104.3
PSA (Ų)
0.37
QED
1
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H24Cl2N6O3S
MW 559.48
Aromatic Rings 4
Heavy Atoms 37
NP-Likeness -1.31

Activity Summary

IC50 29 meas. best 8.82

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Fibroblast growth factor receptor 3
CHEMBL2742
IC50 8.82 8.2513 1.5 8
Vascular endothelial growth factor receptor 3
CHEMBL1955
IC50 8.68 8.68 2.1 1
Fibroblast growth factor receptor 2
CHEMBL4142
IC50 8.15 8.15 7.0 1
RT112/84
CHEMBL6066783
IC50 8.05 7.91 9.0 2
RT-4
CHEMBL614884
IC50 8.0 8.0 10.0 1
Fibroblast growth factor receptor 4
CHEMBL3973
IC50 7.96 7.96 11.0 1
Unchecked
CHEMBL612545
IC50 7.96 7.1983 11.0 6
Tyrosine-protein kinase JAK2
CHEMBL2971
IC50 7.44 7.44 36.0 1
Leukocyte tyrosine kinase receptor
CHEMBL5627
IC50 7.19 7.19 65.0 1
Fibroblast growth factor receptor 1
CHEMBL3650
IC50 6.97 6.97 108.0 1
KG-1
CHEMBL612264
IC50 6.96 6.96 109.0 1
Vascular endothelial growth factor receptor 1
CHEMBL1868
IC50 6.7 6.7 201.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 6.69 6.69 206.0 1
DMS-114
CHEMBL614642
IC50 6.69 6.69 205.0 1
Vascular endothelial growth factor receptor 2
CHEMBL279
IC50 6.49 6.49 325.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.03 5.03 9300.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1734.0 ng.hr.mL-1 Rattus norvegicus
AUC 3355.0 ng.hr.mL-1 Rattus norvegicus
AUC 5930.0 ng.hr.mL-1 Canis lupus familiaris
AUC 58300.0 ng.hr.mL-1 Canis lupus familiaris
AUC 1500.0 ng.hr.mL-1 Macaca mulatta
AUC 15900.0 ng.hr.mL-1 Macaca mulatta
CL 14.0 mL.min-1.kg-1 Homo sapiens
CL 17.5 mL.min-1.kg-1 Rattus norvegicus
CL 2.68 mL.min-1.kg-1 Canis lupus familiaris
CL 11.07 mL.min-1.kg-1 Macaca mulatta
Cmax 0.802 ug.mL-1 Rattus norvegicus
Cmax 3.09 ug.mL-1 Canis lupus familiaris
Cmax 1.21 ug.mL-1 Macaca mulatta
F 39.0 % Rattus norvegicus
F 98.0 % Canis lupus familiaris
F 106.0 % Macaca mulatta
T1/2 1.667 hr Homo sapiens
T1/2 1.667 hr Mus musculus
T1/2 1.667 hr Canis lupus familiaris
T1/2 1.233 hr Rattus norvegicus
T1/2 1.93 hr Rattus norvegicus
T1/2 5.52 hr Canis lupus familiaris
T1/2 24.8 hr Canis lupus familiaris
T1/2 1.17 hr Macaca mulatta
Tmax 4.0 hr Rattus norvegicus
Tmax 6.0 hr Canis lupus familiaris
Tmax 6.0 hr Macaca mulatta
Vd 2.5 L.kg-1 Rattus norvegicus
Vd 1.12 L.kg-1 Canis lupus familiaris
Vd 0.94 L.kg-1 Macaca mulatta

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Fibroblast growth factor receptor 3 IC50 = 1.5 nM 8.82 Inhibition of FGFR3 V555L mutant (unknown origin) by mobility shift assay 39258897
Fibroblast growth factor receptor 3 IC50 = 1.6 nM 8.8 Inhibition of wild-type FGFR3 (unknown origin) by mobility shift assay 39258897
Fibroblast growth factor receptor 3 IC50 = 2.0 nM 8.7 Inhibition of FGFR3 V555M mutant (unknown origin) by mobility shift assay 39258897
Vascular endothelial growth factor receptor 3 IC50 = 2.1 nM 8.68 Inhibition of human FLT4 by KINOMEscan analysis 39258897
Fibroblast growth factor receptor 3 IC50 = 2.3 nM 8.64 Inhibition of FGFR3 K650M mutant (unknown origin) by mobility shift assay 39258897
Fibroblast growth factor receptor 3 IC50 = 2.8 nM 8.55 Inhibition of FGFR3 K650E mutant (unknown origin) by mobility shift assay 39258897
Fibroblast growth factor receptor 2 IC50 = 7.0 nM 8.15 Inhibition of human FGFR2 by KINOMEscan analysis 39258897
RT112/84 IC50 = 9.0 nM 8.05 Inhibition of cell viability in human RT112/84 cells harboring FGFR3/TACC3 fusio... 39258897
RT-4 IC50 = 10.0 nM 8.0 Inhibition of cell viability in human RT-4 cells harboring FGFR3/TACC3 fusion in... 39258897
Unchecked IC50 = 11.0 nM 7.96 Inhibition of recombinant FGFR3/BAIAP2L1 (unknown origin) transduced in mouse Ba... 39258897
Fibroblast growth factor receptor 4 IC50 = 11.0 nM 7.96 Inhibition of human FGFR4 by KINOMEscan analysis 39258897
Unchecked IC50 = 16.0 nM 7.8 Inhibition of cell viability in human UMUC14 cells harboring FGFR3 S249C mutant ... 39258897
RT112/84 IC50 = 17.0 nM 7.77 Inhibition of cell viability in human RT112/84 cells harboring FGFR3 V555M mutan... 39258897
Fibroblast growth factor receptor 3 IC50 = 21.0 nM 7.68 Inhibition of wild-type FGFR3 (unknown origin) by NanoBRET assay 39258897
Unchecked IC50 = 21.0 nM 7.68 Inhibition of cell viability in human UMUC14 cells harboring FGFR3 V555M mutant ... 39258897
Fibroblast growth factor receptor 3 IC50 = 21.0 nM 7.68 Inhibition of FGFR3 G380R mutant (unknown origin) by NanoBRET assay 39258897
Tyrosine-protein kinase JAK2 IC50 = 36.0 nM 7.44 Inhibition of human JAK2 by KINOMEscan analysis 39258897
Leukocyte tyrosine kinase receptor IC50 = 65.0 nM 7.19 Inhibition of human LTK by KINOMEscan analysis 39258897
Fibroblast growth factor receptor 3 IC50 = 73.0 nM 7.14 Inhibition of FGFR3 N540K mutant (unknown origin) by NanoBRET assay 39258897
Fibroblast growth factor receptor 1 IC50 = 108.0 nM 6.97 Inhibition of human FGFR1 by KINOMEscan analysis 39258897

Literature References

PubMed DOI Target Context # Activities
39258897 10.1021/acs.jmedchem.4c01531 ADMET 39
39258897 10.1021/acs.jmedchem.4c01531 Fibroblast growth factor receptor 3 8
39258897 10.1021/acs.jmedchem.4c01531 Unchecked 7
39258897 10.1021/acs.jmedchem.4c01531 RT112/84 4
39258897 10.1021/acs.jmedchem.4c01531 Vascular endothelial growth factor receptor 2 2
39258897 10.1021/acs.jmedchem.4c01531 Voltage-gated inwardly rectifying potassium channel KCNH2 1
39258897 10.1021/acs.jmedchem.4c01531 DMS-114 1
39258897 10.1021/acs.jmedchem.4c01531 KG-1 1
39258897 10.1021/acs.jmedchem.4c01531 RT-4 1
39258897 10.1021/acs.jmedchem.4c01531 Tyrosine-protein kinase JAK3 1
39258897 10.1021/acs.jmedchem.4c01531 Vascular endothelial growth factor receptor 1 1
39258897 10.1021/acs.jmedchem.4c01531 Fibroblast growth factor receptor 1 1
39258897 10.1021/acs.jmedchem.4c01531 Leukocyte tyrosine kinase receptor 1
39258897 10.1021/acs.jmedchem.4c01531 Tyrosine-protein kinase JAK2 1
39258897 10.1021/acs.jmedchem.4c01531 Fibroblast growth factor receptor 4 1
39258897 10.1021/acs.jmedchem.4c01531 Fibroblast growth factor receptor 2 1
39258897 10.1021/acs.jmedchem.4c01531 Vascular endothelial growth factor receptor 3 1

Data from ChEMBL 36 via Core Engine