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Compound Detail

CHEMBL4748740

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COc1cc(OCc2ccnc(Nc3cnn(C)c3)n2)cc2sc(N[C@H]3CCCC[C@@H]3O)nc12

Basic Information

ChEMBL ID CHEMBL4748740
Phase Preclinical
Structure Type MOL
InChI Key MUHWRSWKWURVPP-ROUUACIJSA-N
7
Targets
11
Activities
2
Assay Types
23
PK Parameters
20
Publications
0
Known Names

Molecular Properties

481.6
MW (Da)
3.87
ALogP
11
HBA
3
HBD
119.2
PSA (Ų)
0.34
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C23H27N7O3S
MW 481.58
Aromatic Rings 4
Heavy Atoms 34
NP-Likeness -1.61

Activity Summary

IC50 6 meas. best 8.77
Kd 5 meas. best 9.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Macrophage colony-stimulating factor 1 receptor
CHEMBL1844
Kd 9.0 9.0 1.0 1
Macrophage colony-stimulating factor 1 receptor
CHEMBL1844
IC50 8.77 8.27 1.7 2
Macrophage colony-stimulating factor 1 receptor
CHEMBL5570
IC50 8.15 8.15 7.0 1
Platelet-derived growth factor receptor beta
CHEMBL1913
Kd 6.35 6.35 450.0 1
Platelet-derived growth factor receptor alpha
CHEMBL2007
Kd 5.72 5.72 1900.0 1
Panc02
CHEMBL4483283
IC50 5.52 5.135 3000.0 2
Platelet-derived growth factor receptor beta
CHEMBL1913
IC50 5.45 5.45 3560.0 1
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
Kd 5.02 5.02 9500.0 1
Mast/stem cell growth factor receptor Kit
CHEMBL1936
Kd 4.77 4.77 17000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 14.0 mL.min-1.kg-1 Mus musculus
CL 21.0 mL.min-1.kg-1 Mus musculus
CL 15.0 mL.min-1.kg-1 Rattus norvegicus
CL 64.0 mL.min-1.kg-1 Canis lupus familiaris
CL 37.0 mL.min-1.kg-1 Macaca fascicularis
CL 32.0 mL.min-1.kg-1 Homo sapiens
CL 91.0 mL.min-1.kg-1 Mus musculus
CL 38.0 mL.min-1.kg-1 Rattus norvegicus
CL 293.0 mL.min-1.kg-1 Canis lupus familiaris
CL 208.0 mL.min-1.kg-1 Macaca fascicularis
CL 14.0 mL.min-1.kg-1 Homo sapiens
CL 13.0 mL.min-1.kg-1 Rattus norvegicus
CL 30.0 mL.min-1.kg-1 Canis lupus familiaris
CL 7.2 mL.min-1.kg-1 Macaca fascicularis
F 100.0 % Mus musculus
F 81.0 % Rattus norvegicus
F 37.0 % Canis lupus familiaris
F 21.0 % Macaca fascicularis
Fu 0.065 - Homo sapiens
T1/2 2.2 hr Mus musculus
T1/2 1.7 hr Rattus norvegicus
T1/2 1.37 hr Canis lupus familiaris
T1/2 0.96 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Macrophage colony-stimulating factor 1 receptor Kd = 1.0 nM 9.0 Binding affinity to human wild type CSF1R (I564 to S939 residues) expressed in b... 32787110
Macrophage colony-stimulating factor 1 receptor IC50 = 1.7 nM 8.77 Inhibition of AlexaFluor-labeled tracer 236 binding to recombinant human His-tag... 32787110
Macrophage colony-stimulating factor 1 receptor IC50 = 7.0 nM 8.15 Inhibition of CSF1R in mouse NFS-60 cells assessed as reduction in CSF-induced c... 32787110
Macrophage colony-stimulating factor 1 receptor IC50 = 17.0 nM 7.77 Inhibition of CSF1R phosphorylation in M-CSF induced human THP1 cells incubated ... 32787110
Platelet-derived growth factor receptor beta Kd = 450.0 nM 6.35 Binding affinity to human wild type PDGFRbeta (V582 to Y1009 residues) expressed... 32787110
Platelet-derived growth factor receptor alpha Kd = 1900.0 nM 5.72 Binding affinity to human wild type PDGFRalpha (V575 to D1002 residues) expresse... 32787110
Panc02 IC50 = 3000.0 nM 5.52 Antitumour activity against mouse Panc02 cells implanted in po dosed C57BL/6 mou... 32787110
Platelet-derived growth factor receptor beta IC50 = 3560.0 nM 5.45 Inhibition of human PDGFRbeta phosphorylation in PDGF-DD induced human HEK293-Te... 32787110
Receptor-type tyrosine-protein kinase FLT3 Kd = 9500.0 nM 5.02 Binding affinity to human wild type FLT3 (V592 to Y969 residues) expressed in ba... 32787110
Mast/stem cell growth factor receptor Kit Kd = 17000.0 nM 4.77 Binding affinity to c-Kit (unknown origin) by kinome scan assay 32787110
Panc02 IC50 = 18000.0 nM 4.75 Antitumour activity against mouse Panc02 cells implanted in po dosed C57BL/6 mou... 32787110

Literature References

PubMed DOI Target Context # Activities
32787110 10.1021/acs.jmedchem.0c00936 ADMET 32
32787110 10.1021/acs.jmedchem.0c00936 Macrophage colony-stimulating factor 1 receptor 5
32787110 10.1021/acs.jmedchem.0c00936 Unchecked 5
32787110 10.1021/acs.jmedchem.0c00936 Mast/stem cell growth factor receptor Kit 4
32787110 10.1021/acs.jmedchem.0c00936 MC-38 4
32787110 10.1021/acs.jmedchem.0c00936 Tyrosine-protein kinase ABL1 4
32787110 10.1021/acs.jmedchem.0c00936 Platelet-derived growth factor receptor beta 3
32787110 10.1021/acs.jmedchem.0c00936 Epidermal growth factor receptor 2
32787110 10.1021/acs.jmedchem.0c00936 Serine/threonine-protein kinase B-raf 2
32787110 10.1021/acs.jmedchem.0c00936 Panc02 2
32787110 10.1021/acs.jmedchem.0c00936 Platelet-derived growth factor receptor alpha 2
32787110 10.1021/acs.jmedchem.0c00936 Receptor-type tyrosine-protein kinase FLT3 2
32787110 10.1021/acs.jmedchem.0c00936 Activin receptor type-1B 1
32787110 10.1021/acs.jmedchem.0c00936 Atypical kinase COQ8A, mitochondrial 1
32787110 10.1021/acs.jmedchem.0c00936 RAC-alpha serine/threonine-protein kinase 1
32787110 10.1021/acs.jmedchem.0c00936 RAC-beta serine/threonine-protein kinase 1
32787110 10.1021/acs.jmedchem.0c00936 ALK tyrosine kinase receptor 1
32787110 10.1021/acs.jmedchem.0c00936 Aurora kinase A 1
32787110 10.1021/acs.jmedchem.0c00936 Aurora kinase B 1
32787110 10.1021/acs.jmedchem.0c00936 Tyrosine-protein kinase receptor UFO 1

Data from ChEMBL 36 via Core Engine