BMS-303141 (BMS303141) is a novel, potent, cell-permeable ATP-citrate lyase (ACL) inhibitor with lipid-lowering effects. It inhibits ACL with an IC50 value of 0.13 μM. BMS-303141 inhibits lipid synthesis in HepG2 cells with an IC50 of 8 μM, and lowers plasma triglycerides in a murine hyperlipdemia model. In HepG2 cells, BMS-303141 shows inhibition of total lipid syntheses with an IC50 of 8 μM. BMS-303141 shows no cytotoxicity up to 50 lM under a cell based Alamar Blue cytotoxicity assay, indicating the observed inhibition of lipid synthesis is not a result of compound-induced cytotoxicity.

Physicochemical Properties

Molecular Formula	C₁₉H₁₅CL₂NO₄S
Molecular Weight	424.3
Exact Mass	423.009
Elemental Analysis	C, 53.78; H, 3.56; Cl, 16.71; N, 3.30; O, 15.08; S, 7.56
CAS #	943962-47-8
Related CAS #	943962-47-8
PubChem CID	16747776
Appearance	white to off-white solid powder
Density	1.5±0.1 g/cm3
Boiling Point	594.9±60.0 °C at 760 mmHg
Flash Point	313.6±32.9 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.653
LogP	5.39
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	579
Defined Atom Stereocenter Count	0
SMILES	O=S(C1C(O)=C(Cl)C=C(Cl)C=1)(NC1C(OC)=CC=C(C2C=CC=CC=2)C=1)=O
InChi Key	SIIPNDKXZOTLEA-UHFFFAOYSA-N
InChi Code	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
Chemical Name	3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide
Synonyms	BMS-303141; BMS303141; BMS 303141
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	BMS-303141 inhibits total lipid synthesis in HepG2 cells, with an IC50 of 8 μM. According to a cell-based Alamar Blue cytotoxicity assay, BMS-303141 exhibits no cytotoxicity up to 50 lM, suggesting that compound-induced cytotoxicity is not the cause of the observed inhibition of lipid synthesis[1].
ln Vivo	In high-fat fed mice, BMS-303141 administered orally over an extended period of time reduces plasma cholesterol and triglycerides by approximately 20–30% and fasting plasma glucose by 30–50%. After receiving BMS-303141 for an extended period of time, there is a gradual inhibition of weight gain and a decrease in adiposity without any discernible changes in food intake. BMS-303141 exhibits a 2.1-hour half-life, despite its 55% oral bioavailability[1].
Animal Protocol	10 or 100 mg/kg; oral dose high-fat fed mice
References	[1]. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3208-11.
Additional Infomation	3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide is a member of biphenyls.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 47 mg/mL Water:<1 mg/mL Ethanol: N/A

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.89 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.89 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (5.89 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3568 mL	11.7841 mL	23.5682 mL
	5 mM	0.4714 mL	2.3568 mL	4.7136 mL
	10 mM	0.2357 mL	1.1784 mL	2.3568 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.