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Compound Detail

CHEMBL3945199

BMS-852927
Phase I
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Phase I
CC(C)(O)c1cn(-c2ccc(-c3cc(F)c(CO)c(S(C)(=O)=O)c3)cc2F)c(C(C)(C)c2c(Cl)cccc2Cl)n1

Basic Information

ChEMBL ID CHEMBL3945199
Name BMS-852927
Phase Phase I
Structure Type MOL
InChI Key HNAJDMYOTDNOBK-UHFFFAOYSA-N

Known Names

Bms-852927 EXEL-04541041 XL-041 XL-652
6
Targets
12
Activities
3
Assay Types
3
PK Parameters
12
Publications
4
Known Names
1
Indications
2
Mechanisms

Molecular Properties

609.5
MW (Da)
6.57
ALogP
6
HBA
2
HBD
92.4
PSA (Ų)
0.25
QED
2
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral

Extended Properties

Molecular Formula C29H28Cl2F2N2O4S
MW 609.52
Aromatic Rings 4
Heavy Atoms 40
NP-Likeness -0.78

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
LXR-beta modulator MODULATOR Oxysterols receptor LXR-beta
LXR-alpha modulator MODULATOR Oxysterols receptor LXR-alpha

Indications

Hypercholesterolemia

Activity Summary

EC50 9 meas. best 9.22
Ki 2 meas. best 7.92
IC50 1 meas. best 7.16

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Oxysterols receptor LXR-beta
CHEMBL4093
EC50 9.22 8.135 0.6 6
Unchecked
CHEMBL612545
EC50 8.3 8.3 5.0 1
Oxysterols receptor LXR-alpha
CHEMBL2808
EC50 8.1 8.1 8.0 1
Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-beta
CHEMBL3430878
Ki 7.92 7.92 12.0 1
Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-alpha
CHEMBL3430879
Ki 7.72 7.72 19.0 1
Oxysterols receptor LXR-alpha
CHEMBL2808
IC50 7.16 7.16 69.0 1
Nuclear receptor subfamily 1 group I member 2
CHEMBL3401
EC50 6.0 6.0 1000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.0 mL.min-1.kg-1 Macaca fascicularis
T1/2 12.0 hr Macaca fascicularis
T1/2 10.0 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Oxysterols receptor LXR-beta EC50 = 0.6 nM 9.22 Agonist activity at LXR-beta in human HeLa cells assessed as induction of ABCA1 ... 27994765
Unchecked EC50 = 5.0 nM 8.3 Agonist activity at LXR-beta in cynomolgus monkey whole blood assessed as ABCA1 ... 27994765
Oxysterols receptor LXR-alpha EC50 = 8.0 nM 8.1 Agonist activity at human LXR-alpha expressed in African green monkey CV1 cells ... 27994765
Oxysterols receptor LXR-beta EC50 = 9.0 nM 8.05 Agonist activity at LXR-beta in human whole blood assessed as ABCA1 gene inducti... 27994765
Oxysterols receptor LXR-beta EC50 = 10.0 nM 8.0 Agonist activity at LXR-beta in human whole blood assessed as ABCG1 gene inducti... 27994765
Oxysterols receptor LXR-beta EC50 = 11.0 nM 7.96 ligand sensing assay (LiSA): As used herein, reference to the activity of an LXR... -
Oxysterols receptor LXR-beta EC50 = 11.0 nM 7.96 ligand sensing assay (LiSA): As used herein, reference to the activity of an LXR... -
Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-beta Ki = 12.0 nM 7.92 Displacement of [3H]-24,25-epoxycholesterol from human LXRbeta/RXRalpha expresse... 27994765
Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-alpha Ki = 19.0 nM 7.72 Displacement of [3H]-24,25-epoxycholesterol from human LXRalpha/RXRalpha express... 27994765
Oxysterols receptor LXR-beta EC50 = 24.0 nM 7.62 Agonist activity at human LXR-beta expressed in African green monkey CV1 cells m... 27994765
Oxysterols receptor LXR-alpha IC50 = 69.0 nM 7.16 Antagonist activity at human LXR-alpha expressed in African green monkey CV1 cel... 27994765
Nuclear receptor subfamily 1 group I member 2 EC50 = 1000.0 nM 6.0 Agonist activity at human PXR expressed in human HepG2 cells assessed as inducti... 27994765

Literature References

PubMed DOI Target Context # Activities
27994765 10.1021/acsmedchemlett.6b00234 Oxysterols receptor LXR-beta 9
27994765 10.1021/acsmedchemlett.6b00234 ADMET 6
27994765 10.1021/acsmedchemlett.6b00234 Oxysterols receptor LXR-alpha 4
27994765 10.1021/acsmedchemlett.6b00234 NON-PROTEIN TARGET 4
27994765 10.1021/acsmedchemlett.6b00234 Cynomolgus monkey 3
27994765 10.1021/acsmedchemlett.6b00234 Nuclear receptor subfamily 1 group I member 2 2
27994765 10.1021/acsmedchemlett.6b00234 Unchecked 2
27994765 10.1021/acsmedchemlett.6b00234 Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-beta 1
27994765 10.1021/acsmedchemlett.6b00234 Retinoic acid receptor RXR-alpha/oxysterols receptor LXR-alpha 1
27994765 10.1021/acsmedchemlett.6b00234 Alpha-1-acid glycoprotein 1 1
27994765 10.1021/acsmedchemlett.6b00234 Albumin 1
30004226 10.1021/acs.jmedchem.8b00045 Homo sapiens 1

Data from ChEMBL 36 via Core Engine