(R)-CR8
(Synonyms: (2R)-2-[[9-异丙基-6-[[[4-(2-吡啶基)苯基]甲基]氨基]-9H-嘌呤-2-基]氨基]-1-丁醇,CR8, (R)-Isomer) 目录号 : GC41716
An inhibitor of cyclin-dependent kinases
Cas No.:294646-77-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression and are therefore promising targets for cancer therapy. (R)-CR8 is a second-generation analog of (R)-roscovitine that inhibits Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, Cdk5/p25, and Cdk9/cyclin T with IC50 values of 0.09, 0.072, 0.041, 0.11, and 0.18 μM, respectively. (R)-CR8 has 2- to 4-fold improved potency for the inhibition of CDKs over (R)-roscovitine and can inhibit the proliferation of various cancer cell lines with ~40-fold more potency than (R)-roscovitine (IC50s ~ 0.39 versus 27.8 μM, respectively). (R)-CR8 also inhibits casein kinase 1 (CK1δ/ε) with an IC50 value of 0.40 μM and inhibits GSK3α/β with an IC50 value of 12 μM.
| Cas No. | 294646-77-8 | SDF | |
| 别名 | (2R)-2-[[9-异丙基-6-[[[4-(2-吡啶基)苯基]甲基]氨基]-9H-嘌呤-2-基]氨基]-1-丁醇,CR8, (R)-Isomer | ||
| Canonical SMILES | CC(C)N(C=N1)C2=C1C(NCC3=CC=C(C4=NC=CC=C4)C=C3)=NC(N[C@H](CC)CO)=N2 | ||
| 分子式 | C24H29N7O | 分子量 | 431.5 |
| 溶解度 | DMSO : 50 mg/mL (115.87 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.3175 mL | 11.5875 mL | 23.175 mL |
| 5 mM | 0.4635 mL | 2.3175 mL | 4.635 mL |
| 10 mM | 0.2317 mL | 1.1587 mL | 2.3175 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。
CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases
Oncogene 2008 Oct 2;27(44):5797-807.PMID:18574471DOI:10.1038/onc.2008.191.
Among the ten pharmacological inhibitors of cyclin-dependent kinases (CDKs) currently in clinical trials, the purine roscovitine (CYC202, Seliciclib) is undergoing phase 2 trials against non-small-cell lung and nasopharyngeal cancers. An extensive medicinal chemistry study, designed to generate more potent analogues of roscovitine, led to the identification of an optimal substitution at the N6 position (compound CR8). An extensive selectivity study (108 kinases) highlights the exquisite selectivity of CR8 for CDK1/2/3/5/7/9. CR8 was 2- to 4-fold more potent than (R)-roscovitine at inhibiting these kinases. Cocrystal structures of (R)-CR8 and (R)-roscovitine with pCDK2/cyclin A showed that both inhibitors adopt essentially identical positions. The cellular effects of CR8 and (R)-roscovitine were investigated in human neuroblastoma SH-SY5Y cells. CR8 inhibited the phosphorylation of CDK1 and 9 substrates, with a 25-50 times higher potency compared to (R)-roscovitine. CR8 was consistently more potent than (R)-roscovitine at inducing apoptotic cell death parameters: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium reduction (40-fold), lactate dehydrogenase release (35-fold), caspases activation (68-fold) and poly-(ADP-ribose)polymerase cleavage (50-fold). This improved cell death-inducing activity of CR8 over (R)-roscovitine was observed in 25 different cell lines. Altogether these results show that second-generation analogues of (R)-roscovitine can be designed with improved antitumor potential.
Visualization of global RNA synthesis in a human (mini-) organ in situ by click chemistry
Biotechniques 2018 Aug;65(2):97-100.PMID:30091388DOI:10.2144/btn-2018-0025.
RNA synthesis can be detected by 5-ethynyl uridine (EU) incorporation and click chemistry. Despite identifying a fundamental functional process, this technique has yet to be widely applied to complex human tissue systems. By incorporating EU into human hair follicle (HF) organs cultured ex vivo, nascent RNA synthesis was detected in situ. EU differentially incorporated across the HF epithelium. Interestingly, RNA synthesis did not correlate with protein synthesis, proliferation or epithelial progenitor cell marker expression. By treating human HFs with the cytotoxic cell cycle inhibitor (R)-CR8, which inhibits transcriptional regulators CDK7 and CDK9, it was further shown that this technique can be used to sensitively detect changes in global RNA synthesis in situ. Together, this work delineates new insights into nascent RNA synthesis within a human (mini)- organ and describes a novel read-out parameter that will enrich future ex vivo human tissue research studies.