BSJ-4-116 是由Cereblon配体和CDK配体相连的 PROTAC。BSJ-4-116 是一种高效且选择性的CDK12降解剂，IC50为 6 nM。BSJ-4-116 通过提前终止转录来下调 DDR 基因，主要是通过增加聚腺苷酸化。BSJ-4-116 单独或与聚(ADP-核糖)聚合酶抑制剂 Olaparib (HY-10162) 联合使用时表现出有效的抗增殖作用。
| 生物活性 | BSJ-4-116 is aPROTACconnected by ligands forCereblonandCDK. BSJ-4-116 is a highly potent and selectiveCDK12degrader (PROTAC) with anIC50of 6 nM. BSJ-4-116 downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation). BSJ-4-116 exhibits potent antiproliferative effects, alone and in combination with the poly(ADP-ribose) polymerase inhibitor Olaparib (HY-10162)[1]. |
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体外研究
(In Vitro) | BSJ-4-116 (10-10000 nM; 72 hours) exhibits potent antiproliferative effects in Kelly CDK12C1039F[1].
BSJ-4-116 (50 nM; 6-24 hours) decreases the level of CDK12 protein, regardless of the mutational status of the cell line[1].
BSJ-4-116 inhibits the growth of T-ALL cells (Jurkat and MOLT-4 cells) and sensitizes them to PARP inhibition[1].
BSJ-4-116 regulates DDR genes via poly(adenylation). BSJ-4-116 overcomes CDK12C1039Fmutation. BSJ-4-116 represents the first example of resistance to a bivalent degrader molecule that is a consequence of an acquired point mutation in the target protein[1].
Cell Proliferation Assay[1] | Cell Line: | Parental Kelly and CDK12C1039Fcells | | Concentration: | 10-10000 nM | | Incubation Time: | 72 hours | | Result: | Antiproliferative activity of BSJ-4-116 is independent of the mutational status, and the degrader compounds exhibited improved GR50(growth rate inhibition) values in Kelly CDK12C1039Fcells compared with the parental cell line. |
Western Blot Analysis[1] | Cell Line: | Parental and CDK12C1039F(KellyCDK12CF)-expressing Kelly cells | | Concentration: | 50 nM | | Incubation Time: | 6-24 hours | | Result: | Led to the same level of CDK12 protein level decrease, regardless of the mutational status of the cell line. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 250 mg/mL(298.55 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.1942 mL | 5.9710 mL | 11.9420 mL | | 5 mM | 0.2388 mL | 1.1942 mL | 2.3884 mL | | 10 mM | 0.1194 mL | 0.5971 mL | 1.1942 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-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；
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此方案可获得 ≥ 2.08 mg/mL (2.48 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (2.48 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (2.48 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 20.8 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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