Uses
GO289, is a new potent and highly selective CK2 inhibitor, which strongly lengthens circadian period. It inhibits multiple phsphorylation sites on clock proteins, including PER2 S693. GO289, also exhibited cell type-dependent inhibition of cancer cell growth that correlated with cellular clock function.
Biological Activity
GO289 is a highly potent and selective casein kinase CK2 (CKII) inhibitor (IC50 = 7 nM/CK2, 13 μM/PIM2, >50 μM/CLK2; <50% inhibition of CK1α/δ/γ and 56 other kinases at 5 μM) th at targets CK2-specific residues (CK2α V66, M163, and H160) with more overall interactions at the CK2 ATP-binding pocket than TBB, DM at & CX-4945. GO289 selectively inhibits cellular CK1 substrates phosphorylation (0.8-8 μM; HEK293T, U2OS), including clock proteins PER2, CRY1, CLOCK & BMAL1, and displays circadian period-lengthening (Bmal1-dLuc USOS EC50 = 3.3 μM) as well as growth inhibitory potency in CK2-dependent human renal cell carcinoma (RCC) cultures.
