BMS-986278
目录号 : GC63895
BMS-986278 是一种具有口服活性、高亲和力、强效的小分子 LPA1 拮抗剂，常用于进行性纤维化间质性肺病的研究。
Cas No.:2170126-74-4
Sample solution is provided at 25 µL, 10mM.
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BMS-986278 is an orally active, high-affinity and potent small molecule LPA1 antagonist that is commonly used in the study of progressive fibrotic interstitial lung disease[1][2].
Cytotoxicity for BMS-986278( 0-100μM;24h,72h ) was not observed in human hepatocytes (IC50 >100 μM)[1]. BMS-986278 is a high-affinity LPA1 antagonist, with Kbs of 6.9 nM and 4.0 nM for human and mouse LPA1 in CHO cells overexpressing LPA1[3].
BMS-986278 (30,100 and 300 mg/kg; 6 months) found centrilobular hepatocyte hypertrophy in the liver and gallbladder at 300 mg/kg/day and a dose-dependent increase in alkaline phosphatase (ALP) at all doses (≤ 2.3-fold), total bilirubin (TBILI) was dose-dependently increased (≤ 3.0-fold) only at the 100 mg/kg/day dose [2].BMS-986278(20, 50 and 100 mg/kg/day；1 month) produced a dose-dependent increase in plasma total bile acid (BA) levels in female monkeys [2].
References：
[1]. Gill MW, Murphy BJ, Cheng PTW, Sivaraman L, Davis M, Lehman-McKeeman L. Mechanism of hepatobiliary toxicity of the LPA1 antagonist BMS-986020 developed to treat idiopathic pulmonary fibrosis: Contrasts with BMS-986234 and BMS-986278. Toxicol Appl Pharmacol. 2022 Mar 1;438:115885.
[2]. Sivaraman L, Gill M, Nelson DM, Chadwick KD. Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA1) antagonists. Toxicol Appl Pharmacol. 2022 Mar 1;438:115846.
[3].Cheng PTW, Kaltenbach RF 3rd, Zhang H, et al.Discovery of an Oxycyclohexyl Acid Lysophosphatidic Acid Receptor 1 (LPA1) Antagonist BMS-986278 for the Treatment of Pulmonary Fibrotic Diseases. J Med Chem. 2021 Nov 11;64(21):15549-15581.
BMS-986278是一种具有口服活性、高亲和力、强效的小分子 LPA1 拮抗剂，常用于进行性纤维化间质性肺病的研究[1][2]。
在人肝细胞中未观察到 BMS-986278（0-100μM；24h、72h）的细胞毒性（IC50 >100 μM）[1]。 BMS-986278 是一种高亲和力 LPA1 拮抗剂，在过表达 LPA1 的 CHO 细胞中，对人和小鼠 LPA1 的 Kbs 分别为 6.9 nM 和 4.0 nM[3]。
BMS-986278（30、100 和 300 mg/kg；6 个月）在 300 mg/kg/day剂量下发现肝脏和胆囊中的中心小叶肝细胞肥大，并且所有剂量下碱性磷酸酶 (ALP) 呈剂量依赖性增加（≤ 2.3 倍），总胆红素 (TBILI) 仅在 100 mg/kg/day 剂量下呈剂量依赖性增加（≤ 3.0 倍）[2]。BMS-986278（20、50 和 100 mg/kg/day；6个月）在雌性猴子中产生剂量依赖性血浆总胆汁酸 (BA) 水平增加[2]。
| Cell experiment [1]: | |
Cell lines | Human hepatocyte |
Preparation Method | The human hepatocyte were treated with BMS-986278(0.1, 1, 10, 30, and 100 μM ) for 24 and 72 h . |
Reaction Conditions | BMS-986278 ( 0.1, 1, 10, 30, and 100 μM ) ;24 and 72h |
Applications | BMS-986278 ( 0.1-100μM;24h,72h ) was not observed in human hepatocytes (IC50 >100 μM). |
| Animal experiment [2]: | |
Animal models | BMS-986278 toxicology studies |
Preparation Method | Female rats were given BMS-986278 (30,100,300 mg/kg; po) for 6-month. |
Dosage form | BMS-986020 (30,100,300 mg/kg; po); 6-month. |
Applications | In the 6-month study, hepatobiliary findings included minimal to mild centrilobular hepatocellular hypertrophy at 300 mg/kg/day, dose-dependent increases in ALP at all doses (≤ 2.3×) and TBILI at 100 mg/kg/day only (≤ 3.0×). |
References: | |
| Cas No. | 2170126-74-4 | SDF | Download SDF |
| 分子式 | C22H31N5O5 | 分子量 | 445.51 |
| 溶解度 | DMSO : 50 mg/mL (112.23 mM) | 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。 |
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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2446 mL | 11.2231 mL | 22.4462 mL |
| 5 mM | 0.4489 mL | 2.2446 mL | 4.4892 mL |
| 10 mM | 0.2245 mL | 1.1223 mL | 2.2446 mL |
| 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 | 只 |
| 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 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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