Home>>Signaling Pathways>> Others>> ATP citrate lyase >>BMS-303141

BMS-303141 Sale

目录号 : GC10884

BMS-303141是一种高效性的可渗透细胞的ATP-柠檬酸裂解酶(ACL)抑制剂,IC50值为0.13μM。

BMS-303141 Chemical Structure

Cas No.:943962-47-8

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥557.00
现货
10mg
¥588.00
现货
25mg
¥1,187.00
现货
50mg
¥2,184.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment [1]:

Cell lines

ESCC cells

Preparation Method

ESCC cells were seeded into 96-well plates with 3×103 cells per well and cultured for 24h. They were treated with different concentrations (0, 10, 20, 30, 40, 50, 60, 70, and 80μM) of BMS-303141 or different concentrations (0, 4, 8, 12, 16, and 20μM) of SIRT2 inhibitor AGK2. CCK-8 solution was added at 24, 48, 72, and 96h, and the absorbance at 450nm was measured with a microplate reader 2h later.

Reaction Conditions

0, 10, 20, 30, 40, 50, 60, 70, and 80μM; 24, 48, 72, and 96h

Applications

BMS-303141 significantly inhibited the survival rate of ESCC cells in a time- and dose-dependent manner.

Animal experiment [2]:

Animal models

BALB/c nude mice

Preparation Method

HepG2 cells (5×107 cells/mouse) were injected subcutaneously into the abdomen of the forelimb of BALB/c nude mice. When the tumor volume reached 100mm3, they were randomly divided into 4 groups (4 mice in each group) and gavaged with normal saline, BMS-303141, sorafenib, and BMS-303141 combined with sorafenib at the same concentration of tumor suspension at a dose of 5mg/kg/day for 8 consecutive days. After 8 days of treatment, the tumor volume was measured every 2 days.

Dosage form

5mg/kg/day for 8 days; p.o.

Applications

Treatment of BMS-303141 alone inhibited HCC cells. Moreover, combined treatment with BMS-303141 and sorafenib markedly reduced HepG2 tumour volume and weight compared to sorafenib alone group.

References:

[1]Zhang X, Xu Y, Li S, et al. SIRT2‐mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma[J]. Journal of Cellular and Molecular Medicine, 2024, 28(6): e18129.

[2]Zheng Y, Zhou Q, Zhao C, et al. ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p‐eIF2α/ATF4/CHOP axis[J]. Journal of Cellular and Molecular Medicine, 2021, 25(3): 1468-1479.

产品描述

BMS-303141 is a highly potent and cell-permeable ATP-citrate lyase (ACL) inhibitor with an IC50 value of 0.13μM[1]. ACL is a cytosolic enzyme responsible for the production of cytosolic acetyl-CoA, a precursor required for the de novo biosynthesis of cholesterol and fatty acids[2]. BMS-303141 can be used to block glycolytic activity and mitochondrial pyruvate carrier activity[3].

In vitro, treatment of ESCC cells with BMS-303141 (0-80μM) for 24-96h significantly inhibited cell survival and significantly reduced ACLY protein levels in a time- and dose-dependent manner[4]. Pretreatment of HUVEC cells with BMS-303141 (10μM) 4h before LPS stimulation reversed the LPS-induced upregulation of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble E-selectin, and monocyte chemoattractant protein-1 (MCP-1) without affecting cell viability[5].

In vivo, oral administration of BMS-303141 (5mg/kg/day) for 8 days inhibited the growth of liver cancer cells in mice bearing HepG2 cell xenografts. Combination therapy of BMS-303141 and sorafenib significantly reduced tumor volume and weight and inhibited the expression of Ki-67 in tumor tissues[6]. Oral treatment of spontaneous type 2 diabetic mice with BMS-303141 (50mg/kg/day) for 30 days reduced the levels of serum lipids and renal lipogenic enzymes acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and HMG-CoA reductase (HMGCR), and alleviated ectopic lipid accumulation (ELA) and inflammation in the kidneys[7].

References:
[1] Li J J, Wang H, Tino J A, et al. 2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors[J]. Bioorganic & medicinal chemistry letters, 2007, 17(11): 3208-3211.
[2] Pinkosky S L, Groot P H E, Lalwani N D, et al. Targeting ATP-citrate lyase in hyperlipidemia and metabolic disorders[J]. Trends in molecular medicine, 2017, 23(11): 1047-1063.
[3] Haggadone M D, Speth J, Hong H, et al. ATP Citrate Lyase Links Increases in Glycolytic Flux to Diminished Release of Vesicular Suppressor of Cytokine Signaling 3 by Alveolar Macrophages[M]//TP2. TP002 IMMUNOLOGY AND INFLAMMATION IN PULMONARY INFECTIONS. American Thoracic Society, 2021: A1268-A1268.
[4] Zhang X, Xu Y, Li S, et al. SIRT2‐mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma[J]. Journal of Cellular and Molecular Medicine, 2024, 28(6): e18129.
[5] Li R, Meng M, Chen Y, et al. ATP-citrate lyase controls endothelial gluco-lipogenic metabolism and vascular inflammation in sepsis-associated organ injury[J]. Cell Death & Disease, 2023, 14(7): 401.
[6] Zheng Y, Zhou Q, Zhao C, et al. ATP citrate lyase inhibitor triggers endoplasmic reticulum stress to induce hepatocellular carcinoma cell apoptosis via p‐eIF2α/ATF4/CHOP axis[J]. Journal of Cellular and Molecular Medicine, 2021, 25(3): 1468-1479.
[7] Zhan Z, Li A, Zhang W, et al. ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model[J]. Frontiers in Endocrinology, 2022, 13: 914865.

BMS-303141是一种高效性的可渗透细胞的ATP-柠檬酸裂解酶(ACL)抑制剂,IC50值为0.13μM[1]。ACL是一种胞浆酶,负责产生胞浆乙酰辅酶A,乙酰辅酶A是胆固醇和脂肪酸从头生物合成所需的前体[2]。BMS-303141可用于阻断糖酵解活性和线粒体丙酮酸载体活性[3]

在体外,BMS-303141(0-80μM)处理ESCC细胞24-96h,以时间和剂量依赖性方式显著抑制了细胞存活率,显著降低了ACLY蛋白水平[4]。在LPS刺激前4h用BMS-303141(10μM)预处理HUVEC细胞,逆转了LPS诱导的可溶性血管细胞粘附分子1(VCAM-1)和可溶性E-选择素以及单核细胞趋化蛋白-1(MCP-1)的上调,且不影响细胞活力[5]

在体内,BMS-303141(5mg/kg/day)通过口服治疗HepG2细胞异种移植小鼠8天,抑制了小鼠的肝癌细胞生长,BMS-303141和索拉非尼联合治疗可显著减小肿瘤体积和重量,抑制了肿瘤组织中Ki-67的表达[6]。BMS-303141(50mg/kg/day)通过口服治疗自发性2型糖尿病小鼠30天,降低了小鼠的血清脂质和肾脏脂肪生成酶乙酰辅酶A羧化酶(ACC)、脂肪酸合酶(FAS)、HMG-CoA还原酶(HMGCR)的水平,减轻了肾脏中的异位脂质积累(ELA)和炎症[7]

Chemical Properties

Cas No. 943962-47-8 SDF
化学名 3,5-dichloro-2-hydroxy-N-(4-methoxy-[1,1'-biphenyl]-3-yl)benzenesulfonamide
Canonical SMILES COC1=C(NS(C2=CC(Cl)=CC(Cl)=C2O)(=O)=O)C=C(C3=CC=CC=C3)C=C1
分子式 C19H15Cl2NO4S 分子量 424.3
溶解度 ≥ 21.2mg/mL in DMSO 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
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
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置