BRD9876 是一种 “rigor” 抑制剂，可将驱动蛋白 5 (Eg5) 锁定在增强微管 (MTs) 结合的状态，从而导致 MT 的捆绑和稳定。BRD9876 与酪氨酸 104 残基相互作用，该残基是 α4-α6 变构结合口袋的一部分。BRD9876 特异性靶向微管结合的 Eg5，选择性抑制 CD34 细胞的骨髓瘤。BRD9876 具有用于多发性骨髓瘤 (MM) 研究的潜力。
| 生物活性 | BRD9876 is the “rigor” inhibitor that lockskinesin-5 (Eg5)in a state with enhanced microtubules (MTs) binding, leading to bundling and stabilization of MTs. BRD9876 interacts with the tyrosine 104 residue that is part of the α4-α6 allosteric binding pocket. BRD9876 specifically targets microtubule-bound Eg5 and selectively inhibits myeloma overCD34cells. BRD9876 has the potential for multiple myeloma (MM) research[1][2][3][4]. |
体外研究
(In Vitro) | BRD9876 (10 μM; 24 hours) reveales rapid arrest of cells at the G2/M phase starting as early as 2h of treatment in MM1S cells[1].
BRD9876 exhibits approximately 3-fold selectivity for MM1S myeloma cells (IC50=3.1 μM) over CD34+ derived hematopoietic cells (IC50=9.1 μM)[1].
BRD9876 (0.1, 1, 10, 100 uM) is able to overcome, in MM1S cells, stromal resistance of bone marrow stromal cells (BMSCs) from MM bone marrow aspirates but only minimal effects are observed with BRD9876 against primary MM cells[1].
BRD9876 is completely ineffective at inhibiting the basal ATPase activity of Eg5, in contrast to loop L5-binding monastrol or α4/α6-binding BI8 which shows greater activity against basal Eg5 ATPase activity[1].
Cell Cycle Analysis[1] | Cell Line: | MM1S cells and CD34 hematopoietic cells | | Concentration: | 10 μM | | Incubation Time: | 24 hours | | Result: | Revealed rapid arrest of cells at the G2/M phase starting as early as 2h of treatment in MM1S cells.
Showed markedly less G2/M arrest in CD34 hematopoietic cells. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(213.40 mM;Need ultrasonic) 配制储备液 | 1 mM | 4.2680 mL | 21.3402 mL | 42.6803 mL | | 5 mM | 0.8536 mL | 4.2680 mL | 8.5361 mL | | 10 mM | 0.4268 mL | 2.1340 mL | 4.2680 mL |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (10.67 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (10.67 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。
*以上所有助溶剂都可在本网站选购。 |
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