BMS 303141 Chemical Properties

Boiling point:

591.5±60.0 °C(Predicted)

Density 

1.462±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble20mg/mL, clear

pka

4.94±0.48(Predicted)

form 

powder

color 

white to beige

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.

InChI

1S/C19H15Cl2NO4S/c1-26-17-8-7-13(12-5-3-2-4-6-12)9-16(17)22-27(24,25)18-11-14(20)10-15(21)19(18)23/h2-11,22-23H,1H3

InChIKey

SIIPNDKXZOTLEA-UHFFFAOYSA-N

SMILES

O=S(NC1=C(OC)C=CC(C2=CC=CC=C2)=C1)(C3=C(O)C(Cl)=CC(Cl)=C3)=O

Safety Information

WGK Germany 

3

Storage Class

11 - Combustible Solids

Hazard Classifications

Aquatic Chronic 4

BMS 303141 Usage And Synthesis

Description

BMS-303141 (943963-47-8) is a potent and selective ATP citrate lyase (ACL) inhibitor, IC50=0.13 μM. Inhibits lipid biosynthesis, IC50=8 μM in HepG2 cells.1,2?Reduces weight gain, lowers plasma cholesterol, triglycerides and glucose in high-fat-fed mice.2?A novel tool compound for exploring the potential of ACL inhibition as a target for metabolic disorders such as obesity and dyslipidemia.2?Impairs proliferation or induces death in androgen-depleted castration resistant prostate cancer cells.3?Reduces cell cycle progression in iBN cells.4

Uses

BMS-303141 has been used for inhibition of ATP citrate lyase in breast cancer cell lines.

Definition

ChEBI: 3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide is a member of biphenyls.

Biochem/physiol Actions

BMS-303141 is a potent inhibitor of ATP citrate lyase (ACL). BMS-303141 inhibits lipid synthesis in HepG2 cells with an IC50 of 8 μM, and lowers plasma triglycerides in a murine hyperlipdemia model.

storage

Store at -20°C

Background

The small-molecule BMS-303141 is a potent inhibitor of ATP-citrate lyase. ACL catalyzes the formation of cytosolic acetyl-CoA and oxaloacetate in the cytosol, which is the key step for fatty acid and cholesterol biosynthesis. BMS-303141 also weakly inhibits acetyl-CoA carboxylase isoforms ACC1 and ACC2. Treatment of high-fat fed mice with BMS-303141 reduced weight gain and decreased levels of plasma cholesterol, triglycerides, and glucose. BMS-303141 treatment of prostate cancer cells impaired cell proliferation or induced death in androgen-depleted, castration-resistant prostate cancer cells. Hepatocellular carcinoma cells responded to treatment with BMS-303141, reducing cell proliferation and promoting apoptosis. BMS-303141 is thought to induce endoplasmic reticulum stress and activate the p-eIF2α/ATF4/CHOP pathway to promote apoptosis. The combined treatment of a mouse xenograft model with BMS-303141 and a protein kinase inhibitor reduced tumor volume and weight.

References

[1] JAMES J. LI . 2-Hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors[J]. Bioorganic & Medicinal Chemistry Letters, 2007, 17 11: Pages 3208-3211. DOI:10.1016/j.bmcl.2007.03.017
[2] ZHENGPING MA  Dong C  Ching Hsuen Chu. A novel direct homogeneous assay for ATP citrate lyase.[J]. Journal of Lipid Research, 2009, 50 10: 2131-2135. DOI:10.1194/jlr.d900008-jlr200
[3] SUPRIYA SHAH. Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.[J]. Oncotarget, 2016: 43713-43730. DOI:10.18632/oncotarget.9666
[4] JESS RHEE R D. Regulation of Lipid Metabolism and Cell Cycle Progression By PU.1 in Myeloid Progenitor Cells[J]. Blood, 2017, 130 1: 2433-2433. DOI:10.1182/blood.v130.suppl\_1.2433.2433

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