JH-XI-10-02 是由Cereblon配体和CDK配体相连的PROTAC，是一种高效的选择性PROTAC CDK8降解剂，IC50值为 159 nM。JH-XI-10-02 降解 CDK8 蛋白，但对其 mRNA 水平没有影响。JH-XI-10-02 对 CDK19 无作用。
| 生物活性 | JH-XI-10-02 is aPROTACconnected by ligands forCereblonandCDK. JH-XI-10-02 is a highly potent and selectivePROTACCDK8degrader, with anIC50of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affectCDK8mRNA levels. JH-XI-10-02 shows no effect onCDK19[1]. |
| IC50& Target[1] | CDK8 159 nM (IC50) | Cereblon |
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体外研究
(In Vitro) | JH-XI-10-02, a bivalent small molecule degrader, recruits the E3 ligase CRL4Cereblon to promote the ubiquitination and proteosomal degradation of CDK8[1].
JH-XI-10-02 (1 μM) induces partial degradation of CDK8 in Jurkat cells upon treatment for 6 h. JH-XI-10-02 (1 μM) induces significant degradation of CDK8 after treatment for 24 h[1].
JH-XI-10-02 induces degradation of CDK8 at 5 μM in WT Molt4 cells, no degradation in CRBN null Molt4 cells at any concentration (0.1-5 μM) in WT Molt4 cells and Molt4 cells where CRBN had been subject to CRISPER/CAS9-mediated deletion for 24 h[1].
Western Blot Analysis[1] | Cell Line: | Jurkat cells | | Concentration: | 1 μM | | Incubation Time: | 6 and 24 hours | | Result: | Partial degradation of CDK8 upon treatment for 6 h at a concentration of 1 μM.
Significant degradation of CDK8 after treatment for 24 h at a concentration of 1 μM. |
Western Blot Analysis[1] | Cell Line: | WT Molt4 and CRBN null Molt4 cells | | Concentration: | 0.1, 0.5, 1, 2, 5 μM | | Incubation Time: | 24 hours | | Result: | Degradation of CDK8 at 5 μM in WT Molt4 cells. There were no degradation in CRBN null Molt4 cells at any concentration. |
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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 : 100 mg/mL(108.68 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.0868 mL | 5.4340 mL | 10.8679 mL | | 5 mM | 0.2174 mL | 1.0868 mL | 2.1736 mL | | 10 mM | 0.1087 mL | 0.5434 mL | 1.0868 mL |
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