(R)-CR8 (CR8) 是 Roscovitine 的第二代类似物，是一种有效的CDK1/2/5/7/9抑制剂。(R)-CR8 (CR8) 抑制 CDK1/cyclin B (IC50=0.09 μM)、CDK2/cyclin A (0.072 μM)、CDK2/cyclin E (0.041 μM)、CDK5/p25 (0.11 μM)、CDK7/cyclin H (1.1 μM)、CDK9/cyclin T (0.18 μM) 和 CK1δ/ε (0.4 μM)。(R)-CR8 (CR8) 诱导细胞凋亡并具有神经保护作用。(R)-CR8 作为一种分子胶降解剂来消耗细胞周期蛋白 K。
| 生物活性 | (R)-CR8 (CR8), a second-generation analog of Roscovitine, is a potentCDK1/2/5/7/9inhibitor. (R)-CR8 inhibits CDK1/cyclin B (IC50=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM) and CK1δ/ε (0.4 μM). (R)-CR8 inducesapoptosisand has neuroprotective effect[1][2]. (R)-CR8 acts as a molecular glue degrader that depletes cyclin K[3]. |
| IC50& Target[1] | Cdk1/cyclin B 0.09 μM (IC50) | cdk2/cyclin A 0.072 μM (IC50) | CDK2/cyclinE 0.041 μM (IC50) | Cdk5/p25 0.11 μM (IC50) | CDK7/cyclin H 1.1 μM (IC50) | CDK9/Cyclin T 0.18 μM (IC50) | CK1δ/ε 0.4 μM (IC50) |
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体外研究
(In Vitro) | (R)-CR8 (CR8) (0.1-100 μM; 48 hours) is a potent inducer of apoptotic cell death with an IC50of 0.49 μM for SH-SY5Y cell line[1].
(R)-CR8 (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage[1].
The CDK-bound form of (R)-CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation[3].
Apoptosis Analysis[1] | Cell Line: | SH-SY5Y cell line | | Concentration: | 0.1, 1, 10, 100 μM | | Incubation Time: | 24 hours | | Result: | Reduced cell survival in a dose-dependent manner. |
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体内研究
(In Vivo) | (R)-CR8 (5 mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment[2].
| Animal Model: | Adult (10 to 12 weeks old) male Sprague-Dawley rats (310 to 330 g)[2] | | Dosage: | i.p. | | Administration: | 5 mg/Kg | | Result: | Resulted in a significant reduction in lesion size. |
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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(231.73 mM;ultrasonic and warming and heat to 60℃) 配制储备液 | 1 mM | 2.3173 mL | 11.5867 mL | 23.1734 mL | | 5 mM | 0.4635 mL | 2.3173 mL | 4.6347 mL | | 10 mM | 0.2317 mL | 1.1587 mL | 2.3173 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。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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