| Description |
CLK8 is a potent and specific CLOCK inhibitor that can disrupt the interaction between CLOCK and BMAL1 and interfere with nuclear translocation of CLOCK. CLK8 can be used for the research of disorders associated with dampened circadian rhythms[1].
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| Related Catalog |
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| Target |
CLOCK[1]
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| In Vitro |
CLK8 (10-40 μM; 4-6 d) 以剂量依赖性方式增强 U2OS 和 NIH 3T3 细胞中 Bmal1-dLuc 信号的振幅，且无周期变化[1]。 CLK8 (10-40 μM) 减少 HEK293T 细胞中 BMAL1-CLOCK 相互作用，而 CLOCK-F80A、K220A 和 BMAL1 之间的相互作用不受影响[1]。 CLK8 (20 μM; 2 d) 减少 U2OS 细胞中 CLOCK 的核定位[1]。
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| In Vivo |
CLK8 (25 mg/kg; a single i.p.) 降低小鼠肝脏全细胞裂解物中的 CLOCK 水平，而 BMAL1 和 CRY1 的水平未改变[1]。 CLK8 (5-1000 mg/kg; i.p.) 在 5 和 25 mg/kg 的剂量下没有表现出死亡或临床症状 (呼吸困难、反射减弱、运动活动减少、立毛、驼背姿势和角膜混浊)[1]。 Animal Model: Male C57BL/6J mice (8 weeks, 18-24 g)[1] Dosage: 25 mg/kg Administration: A single i.p. Result: A decrease in CLOCK levels was detected in whole cell lysates of the mouse livers, whereas the levels of BMAL1 and CRY1 were unaltered. Decreased the abundance of CLOCK in the nucleus. The abundances of cytosolic and nuclear BMAL1 and CRY1 were unaltered. Decreased Cry1 transcriptional level.
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| References |
[1]. Doruk YU, et, al. A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude. J Biol Chem. 2020 Mar 13;295(11):3518-3531.
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