CLK8

• CAT Number: I041974
• CAS Number: 898920-65-5
• Molecular Formula: C29H26N2O6
• Molecular Weight: 498.53
• Purity: ≥95%
• Synonyms: 2-[[2-[(8,8-dimethyl-2-oxo-4-phenyl-9,10-dihydropyrano[2,3-h]chromen-5-yl)oxy]acetyl]amino]benzamide
• InChI: InChI=1S/C29H26N2O6/c1-29(2)13-12-19-22(37-29)15-23(35-16-24(32)31-21-11-7-6-10-18(21)28(30)34)26-20(14-25(33)36-27(19)26)17-8-4-3-5-9-17/h3-11,14-15H,12-13,16H2,1-2H3,(H2,30,34)(H,31,32)
• InChIKey: SVELPNHVEDZZRQ-UHFFFAOYSA-N
• SMILES: CC1(CCC2=C3C(=C(C=C2O1)OCC(=O)NC4=CC=CC=C4C(=O)N)C(=CC(=O)O3)C5=CC=CC=C5)C

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].
CLK8 (10-40 μM; 4-6 d) enhances the amplitude of the Bmal1-dLuc signal in U2OS and NIH 3T3 cells in a dose-dependent manner with no period change[1].
CLK8 (10-40 μM) reduces BMAL1-CLOCK interaction, whereas the interaction between CLOCK-F80A, K220A and BMAL1 is not affected in HEK293T cells[1].
CLK8 (20 μM; 2 d) reduces nuclear localization of CLOCK in U2OS cells[1].
CLK8 (25 mg/kg; a single i.p.) decreases CLOCK levels in whole cell lysates of the mouse livers, whereas the levels of BMAL1 and CRY1 are unaltered[1].
CLK8 (5-1000 mg/kg; i.p.) exhibits no mortality or clinical signs (dyspnea, hyporeflexia, reduced locomotor activity, piloerection, hunched posture, and corneal opacity) at the doses of 5 and 25 mg/kg[1].

Reference

[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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