BMS-303141|943962-47-8|安捷凯

Background

BMS-303141 is a potent inhibitor of ATP-citrate lyase with IC50 value of 0.13 μM [1].

ATP-citrate lyase (ACL) is a cytosolic enzyme that responsible for the production of cytosolic acetyl-CoA, a precursor required for de novo biosyntheses of cholesterol and fatty acids. Inhibition of ACL is used to treat dyslipidemia and obesity [1].

BMS-303141 is a potent ATP-citrate lyase inhibitor. In HepG2 cells, BMS-303141 inhibited total lipid syntheses with IC50 value of 8 μM. Also, BMS-303141 showed no cytotoxicity up to 50 μM [1].

In mice, BMS-303141 exhibited an oral bioavailability of 55%. In high-fat fed mice, BMS-303141 reduced the levels of plasma triglyceride, cholesterol by 20-30% and glucose by 30-50% and inhibited weight gain [1]. BMS-303141 inhibited ACL with IC50 value of 0.94 μM for human ACL in a concentration dependant way [2].

参考文献:
[1].? Li JJ, Wang H, Tino JA, et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett, 2007, 17(11): 3208-3211.
[2].? Ma Z, Chu CH, Cheng D. A novel direct homogeneous assay for ATP citrate lyase. J Lipid Res, 2009, 50(10): 2131-2135.

Protocol

Cell experiment [1]:

Cell lines

HepG2 cells

Preparation method

The solubility of this compound in DMSO is > 21.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

8 μM; 6 hrs

Applications

In HepG2 cells, BMS-303141 inhibited total lipid synthesis with an IC50 value of 8 μM. Moreover, BMS-303141 showed no cytotoxicity up to 50 μM.

Animal experiment [1]:

Animal models

High-fat fed mice

Dosage form

10 and 100 mg/kg; p.o.

Applications

In high-fat fed mice, BMS-303141 modestly reduced both plasma cholesterol and triglyceride 20 days after treatment. In addition, fasting plasma glucose started to decrease from day 7 to completion of the study.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

参考文献:

[1]. Li JJ, Wang H, Tino JA, et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett, 2007, 17(11): 3208-3211.

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BMS-303141

BMS-303141详情

Background

Protocol

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