BMS-986242
目录号 : GC62496
BMS-986242 是一种具有口服活性、强效和选择性的 indoleamine-2,3-dioxygenase 1 (IDO1) 抑制剂。BMS-986242 可用于癌症研究。
Cas No.:1923844-48-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BMS-986242 is an orally active, potent and selective indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor. BMS-986242 can be used for the research of cancer[1].
BMS-986242 is more prone to oxidative metabolism and less susceptible to glucuronidation. BMS-986242 shows IC50>25 μM for all targets except nAChR a1 (IC50=12.3 μM) and nAChR a7 (IC50>6 μM with ∼20 % max inhibition)[1].
BMS-986242 (3~30 mg/kg; p.o.; 0~24 hours) exhibits dose-proportional exposure and a statistically significant reduction in kynurenine concentration in the tumor at all three doses[1].
[1]. Cherney EC, et al. Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1. ACS Med Chem Lett. 2021;12(2):288-294. Published 2021 Jan 28.
| Cas No. | 1923844-48-7 | SDF | |
| 分子式 | C24H24ClFN2O | 分子量 | 410.91 |
| 溶解度 | DMSO : 250 mg/mL (608.41 mM; Need ultrasonic) | 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 | 2.4336 mL | 12.1681 mL | 24.3362 mL |
| 5 mM | 0.4867 mL | 2.4336 mL | 4.8672 mL |
| 10 mM | 0.2434 mL | 1.2168 mL | 2.4336 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1
ACS Med Chem Lett 2021 Jan 28;12(2):288-294.PMID:33603977DOI:10.1021/acsmedchemlett.0c00668.
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase enzyme implicated in cancer immune response. This account details the discovery of BMS-986242, a novel IDO1 inhibitor designed for the treatment of a variety of cancers including metastatic melanoma and renal cell carcinoma. Given the substantial interest around this target for cancer immunotherapy, we sought to identify a structurally differentiated clinical candidate that performs comparably to linrodostat (BMS-986205) in terms of both in vitro potency and in vivo pharmacodynamic effect in a mouse xenograft model. On the basis of its preclinical profile, BMS-986242 was selected as a candidate for clinical development.
Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors
ACS Med Chem Lett 2021 Jun 16;12(7):1143-1150.PMID:34267885DOI:10.1021/acsmedchemlett.1c00236.
IDO1 inhibitors have shown promise as immunotherapies for the treatment of a variety of cancers, including metastatic melanoma and renal cell carcinoma. We recently reported the identification of several novel heme-displacing IDO1 inhibitors, including the clinical molecules linrodostat (BMS-986205) and BMS-986242. Both molecules contain quinolines that, while being present in successful medicines, are known to be potentially susceptible to oxidative metabolism. Efforts to swap this quinoline with an alternative aromatic system led to the discovery of 2,3-disubstituted pyridines as suitable replacements. Further optimization, which included lowering ClogP in combination with strategic fluorine incorporation, led to the discovery of compound 29, a potent, selective IDO1 inhibitor with robust pharmacodynamic activity in a mouse xenograft model.