JH-XI-10-02
目录号 : GC65471
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。
Cas No.:2209085-22-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
CDK8 159nM(IC50) |
Cereblon
|
JH-XI-10-02 is a PROTAC connected by ligands for Cereblon and CDK. JH-XI-10-02 is a highly potent and selective PROTAC CDK8 degrader, with an IC50 of 159 nM. JH-XI-10-02 causes proteasomal degradation, does not affect CDK8 mRNA levels. JH-XI-10-02 shows no effect on CDK19[1].
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].
[1]. Hatcher JM, et al. Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8. ACS Med Chem Lett. 2018 Mar 18;9(6):540-545.
| Cas No. | 2209085-22-1 | SDF | Download SDF |
| 分子式 | C53H69N5O9 | 分子量 | 920.14 |
| 溶解度 | DMSO : 100 mg/mL (108.68 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.0868 mL | 5.434 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 |
| 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。
Development of Highly Potent and Selective Steroidal Inhibitors and Degraders of CDK8
ACS Med Chem Lett 2018 Mar 18;9(6):540-545.PMID:29937979DOI:10.1021/acsmedchemlett.8b00011.
Cortistatin A is a natural product isolated from the marine sponge Corticium simplex and was found to be a potent and selective inhibitor of CDK8. Many synthetic groups have reported total syntheses of Cortistatin A; however, these syntheses require between 16 and 30 steps and report between 0.012-2% overall yields, which is not amenable to large-scale production. Owing to similarities between the complex core of Cortistatin A and the simple steroid core, we initiated a campaign to design simple, more easily prepared CDK8 inhibitors based on a steroid scaffold that would be more convenient for large-scale synthesis. Herein, we report the discovery and optimization of JH-VIII-49, a potent and selective inhibitor of CDK8 with a simple steroid core that has an eight-step synthesis with a 33% overall yield, making it suitable for large-scale preparation. Using this scaffold, we then developed a bivalent small molecule degrader, JH-XI-10-02, that can recruit the E3 ligase CRL4Cereblon to promote the ubiquitination and proteosomal degradation of CDK8.