IC261

IC261 is a small molecule inhibitor that acts as a reversible, ATP-competitive inhibitor of casein kinase 1 (CK1), specifically targeting the CK1δ and CK1ε isoforms with an IC50 of approximately 1 µM for both. It also inhibits CK1α at higher concentrations (IC50 ≈ 16 µM). IC261 is highly selective for these kinases and exhibits minimal activity against other kinases such as PKA, p34cdc2, and p55fyn. Mechanistically, by inhibiting CK1δ/ε activity, IC261 disrupts key processes in cell division including cytokinesis and mitotic checkpoint control. This leads to transient mitotic arrest and can induce apoptosis or postmitotic cell cycle arrest depending on the p53 status of the cells. In cancer models such as colon cancer cells, IC261 reduces proliferation and survival while increasing apoptosis; it also modulates aerobic glycolysis through effects on p53-regulated genes. Additionally, structural studies have shown that IC261 can bind to tubulin at the colchicine binding site[1][3][5][7][8].

Other names

3-[(2,4,6-Trimethoxyphenyl)methylidenyl]-indolin-2-one