(R)-CR8 (trihydrochloride)

生物活性靶点体外研究体内研究 (R)-CR8 (trihydrochloride) 试剂级价格

CAS号:1786438-30-9
英文名:(R)-CR8 (trihydrochloride)
中文名:(R)-CR8 (trihydrochloride)
CBNumber:CB65848911
分子式:C24H30ClN7O
分子量:468
MOL File:1786438-30-9.mol

(R)-CR8 (trihydrochloride)化学性质

储存条件 :Store at -20°C
溶解度 :DMSO: 62.5 mg/mL (115.54 mM)
形态 :Solid
颜色 :White to off-white

(R)-CR8 (trihydrochloride)性质、用途与生产工艺

生物活性 (R)-CR8 (CR8) trihydrochloride 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 trihydrochloride 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 trihydrochloride 诱导细胞凋亡并具有神经保护作用。(R)-CR8 trihydrochloride 作为一种分子胶降解剂来消耗细胞周期蛋白 K。

靶点

CDK1/cyclinB1

0.09 μM (IC ₅₀ )

cdk2/cyclin A

0.072 μM (IC ₅₀ )

CDK2/cyclinE

0.041 μM (IC ₅₀ )

Cdk5/p25

0.11 μM (IC ₅₀ )

CDK7/cyclin H

1.1 μM (IC ₅₀ )

CDK9/Cyclin T

0.18 μM (IC ₅₀ )

CK1δ/ε

0.4 μM (IC ₅₀ )

体外研究

(R)-CR8 (CR8) trihydrochloride (0.1-100 μM; 48 hours) is a potent inducer of apoptotic cell death with an IC ₅₀ of 0.49 μM for SH-SY5Y cell line.
(R)-CR8 trihydrochloride (0.25-10 μM) induces a dose-dependent induction of poly-(ADP-ribose)polymerase (PARP) cleavage.
The CDK-bound form of (R)-CR8 trihydrochloride 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

Apoptosis Analysis

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.

体内研究

(R)-CR8 trihydrochloride (5 mg/Kg; i.p.) results in a significant reduction in lesion size at 28 days in histological assessment.

Animal Model:	Adult (10 to 12 weeks old) male Sprague-Dawley rats (310 to 330 g)
Dosage:	5 mg/Kg
Administration:	i.p.
Result:	Resulted in a significant reduction in lesion size.