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Compound Detail

CHEMBL4553037

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Cc1cn(-c2cc(NC(=O)c3ccc4c(c3)CN(c3cncnc3)C[C@@H]4C)cc(C(F)(F)F)c2)cn1

Basic Information

ChEMBL ID CHEMBL4553037
Phase Preclinical
Structure Type MOL
InChI Key CMJJZRAAQMUAFH-INIZCTEOSA-N
9
Targets
28
Activities
2
Assay Types
18
PK Parameters
20
Publications
0
Known Names

Molecular Properties

492.5
MW (Da)
5.37
ALogP
6
HBA
1
HBD
75.9
PSA (Ų)
0.41
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug Chemical Probe

Extended Properties

Molecular Formula C26H23F3N6O
MW 492.51
Aromatic Rings 4
Heavy Atoms 36
NP-Likeness -1.18

Activity Summary

IC50 16 meas. best 8.54
Kd 12 meas. best 8.33

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
NT-3 growth factor receptor
CHEMBL5608
IC50 8.54 8.03 2.9 2
Discoidin domain-containing receptor 2
CHEMBL5122
IC50 8.46 7.105 3.5 4
BDNF/NT-3 growth factors receptor
CHEMBL4898
IC50 8.44 7.9067 3.6 3
Epithelial discoidin domain-containing receptor 1
CHEMBL5319
Kd 8.33 8.33 4.7 1
Epithelial discoidin domain-containing receptor 1
CHEMBL5319
IC50 8.03 7.5975 9.4 4
NT-3 growth factor receptor
CHEMBL5608
Kd 7.75 7.75 18.0 2
BDNF/NT-3 growth factors receptor
CHEMBL4898
Kd 7.66 7.66 22.0 2
High affinity nerve growth factor receptor
CHEMBL2815
IC50 7.37 6.9633 43.0 3
High affinity nerve growth factor receptor
CHEMBL2815
Kd 7.0 7.0 100.0 1
Cyclin-dependent kinase 11A
CHEMBL5416
Kd 6.43 6.43 370.0 1
Cyclin-dependent kinase 11B
CHEMBL5808
Kd 6.43 6.43 370.0 1
Muscle, skeletal receptor tyrosine-protein kinase
CHEMBL5684
Kd 6.28 6.28 530.0 2
Ephrin type-A receptor 8
CHEMBL4134
Kd 6.26 6.26 550.0 2

Pharmacokinetic Data

Parameter Value Units Species
AUC 236.0 ng.hr.mL-1 Rattus norvegicus
AUC 788.3 ng.hr.mL-1 Rattus norvegicus
AUC 1211.9 ng.hr.mL-1 Mus musculus
AUC 2554.1 ng.hr.mL-1 Mus musculus
CL 293.33 mL.min-1.kg-1 Rattus norvegicus
CL 13.33 mL.min-1.kg-1 Mus musculus
Cmax 693.79 nM Rattus norvegicus
Cmax 961.0 nM Rattus norvegicus
Cmax 4562.34 nM Mus musculus
Cmax 4454.73 nM Mus musculus
F 66.8 % Rattus norvegicus
F 41.6 % Mus musculus
T1/2 1.25 hr Rattus norvegicus
T1/2 1.5 hr Rattus norvegicus
T1/2 0.2 hr Mus musculus
T1/2 1.1 hr Mus musculus
Tmax 1.0 hr Rattus norvegicus
Tmax 0.5 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
NT-3 growth factor receptor IC50 = 2.9 nM 8.54 Affinity Biochemical interaction (Radiometric assay (10 µM ATP, Reaction Biology... -
Discoidin domain-containing receptor 2 IC50 = 3.5 nM 8.46 Affinity Biochemical interaction (Radiometric assay (10 µM ATP, Reaction Biology... -
BDNF/NT-3 growth factors receptor IC50 = 3.6 nM 8.44 Affinity Biochemical interaction (Radiometric assay (10 µM ATP, Reaction Biology... -
Epithelial discoidin domain-containing receptor 1 Kd = 4.7 nM 8.33 Binding affinity to wild type human partial length DDR1 (565 to 876 residues) ex... 27219676
Epithelial discoidin domain-containing receptor 1 IC50 = 9.4 nM 8.03 Inhibition of human recombinant GST-tagged DDR1 (440 to 876 residues) expressed ... 27219676
BDNF/NT-3 growth factors receptor IC50 = 14.2 nM 7.85 Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000... -
Epithelial discoidin domain-containing receptor 1 IC50 = 15.4 nM 7.81 Inhibition of GST-tagged recombinant human DDR1 (440 to 876 amino acids) express... 31310125
NT-3 growth factor receptor Kd = 18.0 nM 7.75 Binding affinity to wild type human partial length TRKC (531 to 825 residues) ex... 27219676
NT-3 growth factor receptor Kd = 18.0 nM 7.75 Binding affinity to TrkC (unknown origin) 31310125
BDNF/NT-3 growth factors receptor Kd = 22.0 nM 7.66 Binding affinity to wild type human partial length TRKB (547 to 838 residues) ex... 27219676
BDNF/NT-3 growth factors receptor Kd = 22.0 nM 7.66 Binding affinity to TrkB (unknown origin) 31310125
Epithelial discoidin domain-containing receptor 1 IC50 = 27.0 nM 7.57 Affinity Biochemical interaction (Radiometric assay (10 µM ATP, Reaction Biology... -
NT-3 growth factor receptor IC50 = 30.2 nM 7.52 Inhibition of His-tagged human TrkC expressed in baculovirus expression system u... 31310125
BDNF/NT-3 growth factors receptor IC50 = 36.8 nM 7.43 Inhibition of His-tagged human TrkB expressed in baculovirus expression system u... 31310125
High affinity nerve growth factor receptor IC50 = 43.0 nM 7.37 Affinity Biochemical interaction (Radiometric assay (10 µM ATP, Reaction Biology... -
High affinity nerve growth factor receptor IC50 = 68.4 nM 7.17 Inhibition of His-tagged human TrkA expressed in baculovirus expression system u... 31310125
High affinity nerve growth factor receptor Kd = 100.0 nM 7.0 Binding affinity to wild type human partial length TRKA (475 to 790 residues) ex... 27219676
Epithelial discoidin domain-containing receptor 1 IC50 = 104.0 nM 6.98 Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000... -
Discoidin domain-containing receptor 2 IC50 = 175.0 nM 6.76 Affinity On-target Cellular interaction (NanoBRET assay (HEK293T cells)) EUB0000... -
Discoidin domain-containing receptor 2 IC50 = 188.0 nM 6.73 Inhibition of human recombinant GST-tagged DDR2 expressed in baculovirus infecte... 27219676

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL4689842 U2OS 261
- 10.6019/CHEMBL4689842 HEK-293T 260
- 10.6019/CHEMBL4689842 Fibroblast 260
27219676 10.1021/acs.jmedchem.6b00140 ADMET 18
- 10.6019/CHEMBL5724558 Colon cancer organoid 12
- 10.6019/CHEMBL5674860 Colon cancer organoid 12
- 10.6019/CHEMBL5724696 U2OS 8
- 10.6019/CHEMBL5608141 Colon cancer organoid 6
- 10.1158/2159-8290.CD-23-0050 Colon cancer organoid 5
27219676 10.1021/acs.jmedchem.6b00140 Unchecked 5
27219676 10.1021/acs.jmedchem.6b00140 Epithelial discoidin domain-containing receptor 1 4
27219676 10.1021/acs.jmedchem.6b00140 Mus musculus 4
31310125 10.1021/acs.jmedchem.9b00365 BDNF/NT-3 growth factors receptor 2
31310125 10.1021/acs.jmedchem.9b00365 NT-3 growth factor receptor 2
27219676 10.1021/acs.jmedchem.6b00140 High affinity nerve growth factor receptor 1
27219676 10.1021/acs.jmedchem.6b00140 Tyrosine-protein kinase ABL1 1
27219676 10.1021/acs.jmedchem.6b00140 BDNF/NT-3 growth factors receptor 1
- 10.1021/acschembio.2c00877 Colon organoid 1
27219676 10.1021/acs.jmedchem.6b00140 Ephrin type-A receptor 8 1
27219676 10.1021/acs.jmedchem.6b00140 Cyclin-dependent kinase 11B 1

Data from ChEMBL 36 via Core Engine