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Purity: ≥98%
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.
| Targets |
ATP-Citrate Lyase (ACL) (IC50 = 40 nM, recombinant ACL enzyme activity assay) [1]
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| 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].
1. ACL enzyme activity inhibition: BMS 303141 dose-dependently inhibited the activity of recombinant human ATP-citrate lyase (ACL). The IC50 value was determined to be 40 nM in a standard enzyme activity assay. It showed no significant inhibition of other related enzymes, including citrate synthase and isocitrate dehydrogenase, at concentrations up to 10 μM, indicating selective inhibition of ACL [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].
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| Enzyme Assay |
1. Recombinant ACL enzyme activity assay: Recombinant human ATP-citrate lyase (ACL) was diluted in assay buffer containing Tris-HCl, MgCl2, and dithiothreitol. Different concentrations of BMS 303141 (0.1-1000 nM) were added to the reaction mixture, followed by the addition of substrates ATP (2 mM) and citrate (5 mM) to initiate the reaction. The reaction was incubated at 37℃ for 60 minutes, and the amount of coenzyme A (CoA) generated was quantified using a colorimetric assay based on the reaction of CoA with 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). The absorbance at 412 nm was measured, and the inhibition rate of ACL activity was calculated. The IC50 value was derived from nonlinear regression analysis of the dose-response curve [1]
2. Enzyme selectivity assay: Recombinant citrate synthase and isocitrate dehydrogenase were used to evaluate the selectivity of BMS 303141 (10 μM) using their respective enzyme activity assay protocols. The inhibition rate of each enzyme was calculated to confirm the selective inhibition of ACL [1] |
| Animal Protocol |
10 or 100 mg/kg; oral dose
high-fat fed mice |
| References | |
| Additional Infomation |
3,5-Dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide belongs to the biphenyl class of compounds.
1. BMS 303141 is a small molecule inhibitor belonging to the 2-hydroxy-N-arylbenzenesulfonamide class, specifically targeting ATP-citrate lyase (ACL). ACL is a key enzyme in de novo lipid synthesis, catalyzing the conversion of citrate and ATP into acetyl-CoA and oxaloacetate [1]. 2. The selective inhibition of ACL by BMS 303141 suggests its potential application value in the treatment of diseases associated with lipid metabolism disorders, such as obesity, type 2 diabetes, and cancer. However, further research is needed on its cellular activity, in vivo efficacy and pharmacokinetic properties to verify its clinical application potential [1] 3. The chemical structure of BMS 303141 has a 2-hydroxy-N-arylbenzenesulfonamide skeleton, which has been optimized to bind to the active site of ACL, thereby endowing it with potent and selective inhibitory activity [1] |
| Molecular Formula |
C₁₉H₁₅CL₂NO₄S
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| Molecular Weight |
424.3
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| Exact Mass |
423.009
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| Elemental Analysis |
C, 53.78; H, 3.56; Cl, 16.71; N, 3.30; O, 15.08; S, 7.56
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| CAS # |
943962-47-8
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| Related CAS # |
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| PubChem CID |
16747776
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| Appearance |
white to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
594.9±60.0 °C at 760 mmHg
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| Flash Point |
313.6±32.9 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.653
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| LogP |
5.39
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
579
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=S(C1C(O)=C(Cl)C=C(Cl)C=1)(NC1C(OC)=CC=C(C2C=CC=CC=2)C=1)=O
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| InChi Key |
SIIPNDKXZOTLEA-UHFFFAOYSA-N
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| 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
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| Chemical Name |
3,5-dichloro-2-hydroxy-N-(2-methoxy-5-phenylphenyl)benzenesulfonamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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