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Compound Detail

CHEMBL5169427

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CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)CC(=O)N3)[C@H]2C[C@H]21)c1ccc(Cl)cc1

Basic Information

ChEMBL ID CHEMBL5169427
Phase Preclinical
Structure Type MOL
InChI Key RXNPEQZHMGFNAY-GEALJGNFSA-N
14
Targets
14
Activities
1
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

483.0
MW (Da)
3.15
ALogP
6
HBA
2
HBD
90.5
PSA (Ų)
0.66
QED
0
Ro5 Violations
6
Rot. Bonds

Drug Information

Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H31ClN6O2
MW 483.02
Aromatic Rings 2
Heavy Atoms 34
NP-Likeness -0.55

Activity Summary

IC50 14 meas. best 10.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
RAC-gamma serine/threonine-protein kinase
CHEMBL4816
IC50 10.0 10.0 0.1 1
RAC-alpha serine/threonine-protein kinase
CHEMBL4282
IC50 9.4 9.4 0.4 1
RAC-beta serine/threonine-protein kinase
CHEMBL2431
IC50 8.2 8.2 6.3 1
LNCaP
CHEMBL612518
IC50 7.3 7.3 50.0 1
T47D
CHEMBL614361
IC50 6.68 6.68 209.4 1
RL95-2
CHEMBL2366168
IC50 6.63 6.63 236.5 1
CAL-51
CHEMBL1075411
IC50 6.61 6.61 243.1 1
Unchecked
CHEMBL612545
IC50 6.59 6.59 258.1 1
C-33-A
CHEMBL2366313
IC50 6.52 6.52 299.9 1
TOV21G
CHEMBL4630716
IC50 6.19 6.19 646.2 1
ZR-75-1
CHEMBL614393
IC50 5.89 5.89 1284.0 1
PC-3
CHEMBL390
IC50 5.63 5.63 2346.7 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.82 4.82 15200.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 4.69 4.69 20600.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 2170.0 ng.hr.mL-1 Mus musculus
AUC 1761.0 ng.hr.mL-1 Rattus norvegicus
AUC 3877.0 ng.hr.mL-1 Rattus norvegicus
AUC 1801.0 ng.hr.mL-1 Rattus norvegicus
AUC 3891.0 ng.hr.mL-1 Rattus norvegicus
AUC 1783.0 ng.hr.mL-1 Macaca fascicularis
AUC 1484.0 ng.hr.mL-1 Macaca fascicularis
AUC 1885.0 ng.hr.mL-1 Macaca fascicularis
AUC 1682.0 ng.hr.mL-1 Macaca fascicularis
AUC 7028.0 ng.hr.mL-1 Mus musculus
AUC 13531.0 ng.hr.mL-1 Mus musculus
AUC 22029.0 ng.hr.mL-1 Mus musculus
CL 0.00358 mL.min-1.kg-1 Mus musculus
CL 0.0127 mL.min-1.kg-1 Mus musculus
CL 0.00606 mL.min-1.kg-1 Rattus norvegicus
CL 0.0122 mL.min-1.kg-1 Rattus norvegicus
CL 0.021 mL.min-1.kg-1 Canis lupus familiaris
CL 0.0169 mL.min-1.kg-1 Canis lupus familiaris
CL 0.049 mL.min-1.kg-1 Macaca fascicularis
CL 0.0252 mL.min-1.kg-1 Macaca fascicularis
CL 0.0152 mL.min-1.kg-1 Homo sapiens
CL 0.00896 mL.min-1.kg-1 Homo sapiens
Cmax 3500.89 nM Rattus norvegicus
Cmax 1459.57 nM Rattus norvegicus
Cmax 1453.36 nM Macaca fascicularis
Cmax 490.66 nM Macaca fascicularis
Cmax 1993.71 nM Mus musculus
Cmax 4093.0 nM Mus musculus
Cmax 6308.23 nM Mus musculus
F 29.7 % Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
RAC-gamma serine/threonine-protein kinase IC50 = 0.1 nM 10.0 Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (... 35679512
RAC-alpha serine/threonine-protein kinase IC50 = 0.4 nM 9.4 Inhibition of recombinant AKT1 (104 to 480 end residues) (unknown origin) cataly... 35679512
RAC-beta serine/threonine-protein kinase IC50 = 6.3 nM 8.2 Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) cataly... 35679512
LNCaP IC50 = 50.0 nM 7.3 Antiproliferative activity against human LNcap assessed as reduction in cell via... 35679512
T47D IC50 = 209.43 nM 6.68 Antiproliferative activity against human T47D habouring PIK3CA mutation/amplicat... 35679512
RL95-2 IC50 = 236.47 nM 6.63 Antiproliferative activity against human RL95-2 habouring PTEN deletion mutant a... 35679512
CAL-51 IC50 = 243.07 nM 6.61 Antiproliferative activity against human CAL-51 habouring PTEN deletion and PIK3... 35679512
Unchecked IC50 = 258.07 nM 6.59 Antiproliferative activity against human COLO-704 habouring PTEN deletion mutant... 35679512
C-33-A IC50 = 299.87 nM 6.52 Antiproliferative activity against human C-33-A habouring PTEN deletion mutant a... 35679512
TOV21G IC50 = 646.23 nM 6.19 Antiproliferative activity against human TOV-21G habouring PTEN deletion and PIK... 35679512
ZR-75-1 IC50 = 1283.97 nM 5.89 Antiproliferative activity against human ZR-75-1 habouring PTEN deletion mutant ... 35679512
PC-3 IC50 = 2346.67 nM 5.63 Antiproliferative activity against human PC-3 habouring PTEN deletion and PIK3CA... 35679512
Cytochrome P450 3A4 IC50 = 15200.0 nM 4.82 Inhibition of CYP3A4 in human liver microsomes at 0.01 to 30 uM using phenacetin... 35679512
Cytochrome P450 2D6 IC50 = 20600.0 nM 4.69 Inhibition of CYP2D6 in human liver microsomes at 0.01 to 30 uM using dextrometh... 35679512

Literature References

PubMed DOI Target Context # Activities
35679512 10.1021/acs.jmedchem.2c00527 ADMET 55
35679512 10.1021/acs.jmedchem.2c00527 LNCaP 22
35679512 10.1021/acs.jmedchem.2c00527 Unchecked 4
35679512 10.1021/acs.jmedchem.2c00527 Serine/threonine-protein kinase AKT 2
35679512 10.1021/acs.jmedchem.2c00527 Ribosomal protein S6 kinase alpha-4 1
35679512 10.1021/acs.jmedchem.2c00527 Cytochrome P450 2D6 1
35679512 10.1021/acs.jmedchem.2c00527 TOV21G 1
35679512 10.1021/acs.jmedchem.2c00527 T47D 1
35679512 10.1021/acs.jmedchem.2c00527 CAL-51 1
35679512 10.1021/acs.jmedchem.2c00527 PC-3 1
35679512 10.1021/acs.jmedchem.2c00527 Protein kinase C alpha type 1
35679512 10.1021/acs.jmedchem.2c00527 Protein kinase C theta type 1
35679512 10.1021/acs.jmedchem.2c00527 Protein kinase C eta type 1
35679512 10.1021/acs.jmedchem.2c00527 ZR-75-1 1
35679512 10.1021/acs.jmedchem.2c00527 Cytochrome P450 3A4 1
35679512 10.1021/acs.jmedchem.2c00527 Cytochrome P450 2C9 1
35679512 10.1021/acs.jmedchem.2c00527 Cytochrome P450 1A2 1
35679512 10.1021/acs.jmedchem.2c00527 Cytochrome P450 2C19 1
35679512 10.1021/acs.jmedchem.2c00527 RAC-gamma serine/threonine-protein kinase 1
35679512 10.1021/acs.jmedchem.2c00527 RAC-beta serine/threonine-protein kinase 1

Data from ChEMBL 36 via Core Engine