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Compound Detail

CHEMBL4761772

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CC(C)(O)C(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12

Basic Information

ChEMBL ID CHEMBL4761772
Phase Preclinical
Structure Type MOL
InChI Key JZUVTKBHDNIOHD-MIZPHKNDSA-N
9
Targets
13
Activities
2
Assay Types
23
PK Parameters
16
Publications
0
Known Names

Molecular Properties

599.5
MW (Da)
5.40
ALogP
4
HBA
2
HBD
83.5
PSA (Ų)
0.36
QED
2
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C26H25F8NO4S
MW 599.54
Aromatic Rings 2
Heavy Atoms 40
NP-Likeness -0.11

Activity Summary

IC50 8 meas. best 8.22
EC50 5 meas. best 8.57

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Nuclear receptor ROR-gamma
CHEMBL1293231
EC50 8.57 8.57 2.7 1
Nuclear receptor ROR-gamma
CHEMBL1741186
EC50 8.44 7.86 3.6 4
Nuclear receptor ROR-gamma
CHEMBL1741186
IC50 8.22 8.22 6.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 4.96 4.96 11000.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.92 4.92 12000.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 4.92 4.92 12000.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.72 4.72 19000.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 4.72 4.72 19000.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 4.7 4.7 20000.0 1
Cytochrome P450 1A2
CHEMBL3356
IC50 4.7 4.7 20000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 19904.73 ng.hr.mL-1 Mus musculus
AUC 10192.18 ng.hr.mL-1 Rattus norvegicus
AUC 35852.49 ng.hr.mL-1 Canis lupus familiaris
AUC 10791.72 ng.hr.mL-1 Macaca fascicularis
CL 3.7 mL.min-1.kg-1 Mus musculus
CL 4.2 mL.min-1.kg-1 Rattus norvegicus
CL 0.8 mL.min-1.kg-1 Canis lupus familiaris
CL 2.7 mL.min-1.kg-1 Macaca fascicularis
Cmax 2200.0 nM Mus musculus
Cmax 1000.0 nM Rattus norvegicus
Cmax 1300.0 nM Canis lupus familiaris
Cmax 1100.0 nM Macaca fascicularis
F 100.0 % Mus musculus
F 65.0 % Rattus norvegicus
F 83.0 % Canis lupus familiaris
F 75.0 % Macaca fascicularis
Fu 0.005 - Homo sapiens
Fu 0.006 - Mus musculus
T1/2 2.0 hr Homo sapiens
T1/2 2.0 hr Mus musculus
T1/2 2.0 hr Rattus norvegicus
T1/2 2.0 hr Canis lupus familiaris
T1/2 2.0 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Nuclear receptor ROR-gamma EC50 = 2.7 nM 8.57 Inverse agonist activity at RORgammat in mouse Th17 cells assessed as inhibition... 33591748
Nuclear receptor ROR-gamma EC50 = 3.6 nM 8.44 Inverse agonist activity at recombinant full-length human Gal4-fused RORgammat e... 33591748
Nuclear receptor ROR-gamma EC50 = 4.0 nM 8.4 Inverse agonist activity at human Gal4-fused RORgammat expressed in human Jurkat... 34055233
Nuclear receptor ROR-gamma IC50 = 6.0 nM 8.22 General RORgamma Gal4 Reporter Assay: Inverse agonist activity of potential liga... -
Nuclear receptor ROR-gamma EC50 = 50.0 nM 7.3 Inverse agonist activity at RORgammat in human whole blood assessed as inhibitio... 34055233
Nuclear receptor ROR-gamma EC50 = 50.0 nM 7.3 Inverse agonist activity at RORgammat in CD3 and CD28-stimulated human whole blo... 33591748
Cytochrome P450 3A4 IC50 = 11000.0 nM 4.96 Inhibition of CYP3A4 (unknown origin) 33591748
Cytochrome P450 2C9 IC50 = 12000.0 nM 4.92 Inhibition of CYP2C9 (unknown origin) 33591748
Cytochrome P450 2C8 IC50 = 12000.0 nM 4.92 Inhibition of CYP2C8 (unknown origin) 33591748
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 19000.0 nM 4.72 Inhibition of human ERG by patch-clamp assay 33591748
Cytochrome P450 2C19 IC50 = 19000.0 nM 4.72 Inhibition of CYP2C19 (unknown origin) 33591748
Cytochrome P450 1A2 IC50 = 20000.0 nM 4.7 Inhibition of CYP1A2 (unknown origin) 33591748
Cytochrome P450 2D6 IC50 = 20000.0 nM 4.7 Inhibition of CYP2D6 (unknown origin) 33591748

Literature References

PubMed DOI Target Context # Activities
33591748 10.1021/acs.jmedchem.0c01992 ADMET 32
33591748 10.1021/acs.jmedchem.0c01992 Mus musculus 24
33591748 10.1021/acs.jmedchem.0c01992 Nuclear receptor ROR-gamma 3
34055233 10.1021/acsmedchemlett.1c00112 Nuclear receptor ROR-gamma 2
33591748 10.1021/acs.jmedchem.0c01992 Nuclear receptor ROR-alpha 1
33591748 10.1021/acs.jmedchem.0c01992 Nuclear receptor ROR-beta 1
33591748 10.1021/acs.jmedchem.0c01992 Nuclear receptor subfamily 1 group I member 2 1
33591748 10.1021/acs.jmedchem.0c01992 Oxysterols receptor LXR-alpha 1
33591748 10.1021/acs.jmedchem.0c01992 Oxysterols receptor LXR-beta 1
33591748 10.1021/acs.jmedchem.0c01992 Voltage-gated inwardly rectifying potassium channel KCNH2 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 1A2 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 2D6 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 2C9 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 3A4 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 2C8 1
33591748 10.1021/acs.jmedchem.0c01992 Cytochrome P450 2C19 1

Data from ChEMBL 36 via Core Engine