BMS-986278 |
| رقم الكتالوجGC63895 |
بي إم إس-986278 هو مضاد فعال لمستقبل حمض الليزوفوسفاتيديك 1 (LPA1)، وله قدرة على التأثير على LPA1 Kb البشرية بتركيز يصل إلى 6.9 نانومتر.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Formula | C22H31N5O5 | M.Wt | 445.51 |
| الذوبان | DMSO : 50 mg/mL (112.23 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 33 reference(s) in Google Scholar.)
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