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Compound Detail

CHEMBL4460552

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C[C@H](NC(=O)c1nc(-c2ncc(-c3ccccc3)s2)sc1C1CC1)c1ccc(C(=O)NO)cc1

Basic Information

ChEMBL ID CHEMBL4460552
Phase Preclinical
Structure Type MOL
InChI Key SELDFFFQCMDDJR-AWEZNQCLSA-N
16
Targets
18
Activities
1
Assay Types
22
PK Parameters
20
Publications
0
Known Names

Molecular Properties

490.6
MW (Da)
5.42
ALogP
7
HBA
3
HBD
104.2
PSA (Ų)
0.24
QED
1
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C25H22N4O3S2
MW 490.61
Aromatic Rings 4
Heavy Atoms 34
NP-Likeness -1.02

Activity Summary

IC50 18 meas. best 8.8

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histone deacetylase 6
CHEMBL1865
IC50 8.8 8.75 1.6 2
Polyamine deacetylase HDAC10
CHEMBL5103
IC50 8.7 8.7 2.0 1
Histone deacetylase 3
CHEMBL1829
IC50 8.52 8.52 3.0 1
Histone deacetylase 1
CHEMBL325
IC50 8.45 8.425 3.6 2
Histone deacetylase 2
CHEMBL1937
IC50 7.88 7.88 13.3 1
Histone deacetylase 8
CHEMBL3192
IC50 7.77 7.77 16.8 1
NCI-N87
CHEMBL614197
IC50 7.55 7.55 28.3 1
T47D
CHEMBL614361
IC50 7.39 7.39 40.8 1
MCF7
CHEMBL387
IC50 7.23 7.23 58.5 1
NCI-H1975
CHEMBL614348
IC50 7.18 7.18 66.4 1
MDA-MB-231
CHEMBL400
IC50 7.12 7.12 76.6 1
Histone deacetylase 11
CHEMBL3310
IC50 7.11 7.11 77.8 1
Bel-7402
CHEMBL614279
IC50 7.09 7.09 80.8 1
EBC-1
CHEMBL4296411
IC50 6.96 6.96 110.0 1
HT-29
CHEMBL384
IC50 6.78 6.78 166.0 1
Histone deacetylase 5
CHEMBL2563
IC50 4.78 4.78 16740.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1075.0 ng.hr.mL-1 Mus musculus
AUC 1248.0 ng.hr.mL-1 Mus musculus
AUC 924.0 ng.hr.mL-1 Mus musculus
AUC 944.0 ng.hr.mL-1 Mus musculus
AUC 105642.0 ng.hr/g Mus musculus
AUC 8795.0 ng.hr/g Mus musculus
AUC 6079.0 ng.hr/g Mus musculus
AUC 5185.0 ng.hr/g Mus musculus
AUC 4692.0 ng.hr/g Mus musculus
AUC 3438.0 ng.hr/g Mus musculus
AUC 2622.0 ng.hr/g Mus musculus
AUC 1964.0 ng.hr/g Mus musculus
AUC 1472.0 ng.hr/g Mus musculus
AUC 698.0 ng.hr/g Mus musculus
AUC 599.0 ng.hr/g Mus musculus
Cmax 281.28 nM Mus musculus
F 34.0 % Mus musculus
MRT 10.4 hr Mus musculus
MRT 5.22 hr Mus musculus
T1/2 8.67 hr Mus musculus
T1/2 4.23 hr Mus musculus
Tmax 0.67 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histone deacetylase 6 IC50 = 1.59 nM 8.8 Inhibition of recombinant His6/GST-tagged human HDAC6 expressed in baculovirus i... 31855601
Polyamine deacetylase HDAC10 IC50 = 1.98 nM 8.7 Inhibition of recombinant human His6/GST-tagged HDAC10 expressed in baculovirus ... 31855601
Histone deacetylase 6 IC50 = 2.0 nM 8.7 Inhibition of HDAC6 (unknown origin) using Ac-peptide as substrate preincubated ... 37708798
Histone deacetylase 3 IC50 = 3.02 nM 8.52 Inhibition of recombinant His6/GST-tagged human HDAC3 expressed in baculovirus i... 31855601
Histone deacetylase 1 IC50 = 3.59 nM 8.45 Inhibition of recombinant His6/GST-tagged human HDAC1 expressed in baculovirus i... 31855601
Histone deacetylase 1 IC50 = 4.0 nM 8.4 Inhibition of human recombinant HDAC1 using Ac-RHKK(Acetyl)-AMC peptide as fluor... 37708798
Histone deacetylase 2 IC50 = 13.26 nM 7.88 Inhibition of recombinant human His6/GST-tagged HDAC2 expressed in baculovirus i... 31855601
Histone deacetylase 8 IC50 = 16.84 nM 7.77 Inhibition of recombinant human His6/GST-tagged HDAC8 expressed in baculovirus i... 31855601
NCI-N87 IC50 = 28.33 nM 7.55 Antiproliferative activity against human NCI-N87 cells assessed as reduction in ... 31855601
T47D IC50 = 40.81 nM 7.39 Antiproliferative activity against human T47D cells assessed as reduction in cel... 31855601
MCF7 IC50 = 58.52 nM 7.23 Antiproliferative activity against human MCF7 cells assessed as reduction in cel... 31855601
NCI-H1975 IC50 = 66.38 nM 7.18 Antiproliferative activity against human NCI-H1975 cells assessed as reduction i... 31855601
MDA-MB-231 IC50 = 76.56 nM 7.12 Antiproliferative activity against human MDA-MB-231 cells assessed as reduction ... 31855601
Histone deacetylase 11 IC50 = 77.82 nM 7.11 Inhibition of recombinant human His6/GST-tagged HDAC11 expressed in baculovirus ... 31855601
Bel-7402 IC50 = 80.79 nM 7.09 Antiproliferative activity against human Bel7402 cells assessed as reduction in ... 31855601
EBC-1 IC50 = 110.0 nM 6.96 Antiproliferative activity against human EBC1 cells assessed as reduction in cel... 31855601
HT-29 IC50 = 166.0 nM 6.78 Antiproliferative activity against human HT-29 cells assessed as reduction in ce... 31855601
Histone deacetylase 5 IC50 = 16740.0 nM 4.78 Inhibition of recombinant N-terminal GST-tagged full length human HDAC5 expresse... 31855601

Literature References

PubMed DOI Target Context # Activities
31855601 10.1021/acs.jmedchem.9b01792 ADMET 80
31855601 10.1021/acs.jmedchem.9b01792 HT-29 10
32791404 10.1016/j.ejmech.2020.112679 HT-29 3
31855601 10.1021/acs.jmedchem.9b01792 Mus musculus 2
31855601 10.1021/acs.jmedchem.9b01792 NAD-dependent protein deacetylase sirtuin-3, mitochondrial 1
31855601 10.1021/acs.jmedchem.9b01792 NCI-N87 1
31855601 10.1021/acs.jmedchem.9b01792 T47D 1
31855601 10.1021/acs.jmedchem.9b01792 MCF7 1
31855601 10.1021/acs.jmedchem.9b01792 EBC-1 1
31855601 10.1021/acs.jmedchem.9b01792 NCI-H1975 1
31855601 10.1021/acs.jmedchem.9b01792 Bel-7402 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 2 1
37708798 10.1016/j.ejmech.2023.115800 Histone deacetylase 6 1
31855601 10.1021/acs.jmedchem.9b01792 NAD-dependent protein deacetylase sirtuin-1 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 11 1
31855601 10.1021/acs.jmedchem.9b01792 Polyamine deacetylase HDAC10 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 9 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 8 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 7 1
31855601 10.1021/acs.jmedchem.9b01792 Histone deacetylase 5 1

Data from ChEMBL 36 via Core Engine