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Compound Detail

CHEMBL4175555

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CS(=O)(=O)Nc1ccc(-c2ccnc(Nc3ccc(N4CCC(C(=O)Nc5ccc(/C=C/C(=O)NO)cc5)CC4)cc3)n2)cc1

Basic Information

ChEMBL ID CHEMBL4175555
Phase Preclinical
Structure Type MOL
InChI Key LUTGPKYBTPTJKM-SYZQJQIISA-N
12
Targets
12
Activities
1
Assay Types
7
PK Parameters
17
Publications
0
Known Names

Molecular Properties

627.7
MW (Da)
4.63
ALogP
9
HBA
5
HBD
165.7
PSA (Ų)
0.10
QED
1
Ro5 Violations
10
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C32H33N7O5S
MW 627.73
Aromatic Rings 4
Heavy Atoms 45
NP-Likeness -1.33

Activity Summary

IC50 12 meas. best 8.1

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Tyrosine-protein kinase JAK2
CHEMBL2971
IC50 8.1 8.1 8.0 1
Histone deacetylase 6
CHEMBL1865
IC50 7.34 7.34 46.0 1
Non-receptor tyrosine-protein kinase TYK2
CHEMBL3553
IC50 7.34 7.34 46.0 1
Tyrosine-protein kinase JAK3
CHEMBL2148
IC50 6.92 6.92 121.0 1
Histone deacetylase 3/NCoR1
CHEMBL3038484
IC50 6.63 6.63 234.0 1
Histone deacetylase 1
CHEMBL325
IC50 6.6 6.6 250.0 1
HEL
CHEMBL613888
IC50 6.47 6.47 340.0 1
Tyrosine-protein kinase JAK1
CHEMBL2835
IC50 6.45 6.45 359.0 1
HL-60
CHEMBL383
IC50 5.82 5.82 1500.0 1
Histone deacetylase 8
CHEMBL3192
IC50 5.22 5.22 6065.0 1
Histone deacetylase 2
CHEMBL1937
IC50 5.13 5.13 7472.0 1
K562
CHEMBL385
IC50 5.06 5.06 8700.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 4470.13 ng.hr.mL-1 Rattus norvegicus
CL 71.6 mL.min-1.g-1 Mus musculus
CL 2246.64 ml/hr/mg Rattus norvegicus
Cmax 2553.65 nM Rattus norvegicus
T1/2 0.3233 hr Mus musculus
T1/2 5.14 hr Rattus norvegicus
Tmax 0.5 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Tyrosine-protein kinase JAK2 IC50 = 8.0 nM 8.1 Inhibition of JAK2 (unknown origin) using FAM-labeled peptide as substrate prein... 29940115
Non-receptor tyrosine-protein kinase TYK2 IC50 = 46.0 nM 7.34 Inhibition of TYK2 (unknown origin) using FAM-labeled peptide as substrate prein... 29940115
Histone deacetylase 6 IC50 = 46.0 nM 7.34 Inhibition of full length human recombinant HDAC6 expressed in Baculovirus infec... 29940115
Tyrosine-protein kinase JAK3 IC50 = 121.0 nM 6.92 Inhibition of JAK3 (unknown origin) using FAM-labeled peptide as substrate prein... 29940115
Histone deacetylase 3/NCoR1 IC50 = 234.0 nM 6.63 Inhibition of human recombinant HDAC3/GST-tagged NCOR1 (397 to 503 residues) co-... 29940115
Histone deacetylase 1 IC50 = 250.0 nM 6.6 Inhibition of full length human recombinant HDAC1 expressed in baculovirus expre... 29940115
HEL IC50 = 340.0 nM 6.47 Antiproliferative activity against human HEL cells after 48 hrs by CCK-8 assay 29940115
Tyrosine-protein kinase JAK1 IC50 = 359.0 nM 6.45 Inhibition of JAK1 (unknown origin) using FAM-labeled peptide as substrate prein... 29940115
HL-60 IC50 = 1500.0 nM 5.82 Antiproliferative activity against human HL60 cells after 48 hrs by CCK-8 assay 29940115
Histone deacetylase 8 IC50 = 6065.0 nM 5.22 Inhibition of full length recombinant C-terminal His tagged human HDAC8 expresse... 29940115
Histone deacetylase 2 IC50 = 7472.0 nM 5.13 Inhibition of recombinant HDAC2 (unknown origin) using (Ac-Leu-Gly-Lys(Ac)-AMC a... 29940115
K562 IC50 = 8700.0 nM 5.06 Antiproliferative activity against human K562 cells after 48 hrs by CCK-8 assay 29940115

Literature References

PubMed DOI Target Context # Activities
29940115 10.1021/acs.jmedchem.8b00393 Candida albicans 16
29940115 10.1021/acs.jmedchem.8b00393 HEL 7
29940115 10.1021/acs.jmedchem.8b00393 Rattus norvegicus 5
29940115 10.1021/acs.jmedchem.8b00393 Mus musculus 4
29940115 10.1021/acs.jmedchem.8b00393 ADMET 2
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 2
29940115 10.1021/acs.jmedchem.8b00393 Tyrosine-protein kinase JAK2 2
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 2 1
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 8 1
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 6 1
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 3/NCoR1 1
29940115 10.1021/acs.jmedchem.8b00393 Non-receptor tyrosine-protein kinase TYK2 1
29940115 10.1021/acs.jmedchem.8b00393 Tyrosine-protein kinase JAK3 1
29940115 10.1021/acs.jmedchem.8b00393 Tyrosine-protein kinase JAK1 1
29940115 10.1021/acs.jmedchem.8b00393 K562 1
29940115 10.1021/acs.jmedchem.8b00393 HL-60 1
29940115 10.1021/acs.jmedchem.8b00393 Histone deacetylase 1 1

Data from ChEMBL 36 via Core Engine