IC261

IC261 (IC-261, SU-5607) is a potent, specific, ATP-competitive CK1delta/epsilon (CK1δ/CK1ε) with IC50 of 1 uM, does not block the activity of α, β and γ isoforms; specifically blocks phosphorylation in vivo of the CK1delta/epsilon phosphorylation sites in p53 in murine SV3T3 cells, inhibits cytokinesis causing a transient mitotic arrest; reduces pancreatic tumour cell growth in vitro and in vivo, decreases the expression levels of several anti-apoptotic proteins and sensitises cells to CD95-mediated apoptosis.(In Vitro):IC261 is a selective, ATP-competitive CK1 inhibitor, with IC50s of 1 μM, 1 μM, 16 μM for Ckiδ, Ckiε and Ckiα1, respectively. IC261 is less active on PKA, p34cdc2, and p55fyn (IC50s > 100 μM). IC261 induces mitotic arrest, spindle defects and centrosome amplification in AC1-M88 cells. IC261 (1 μM) increases G2/M cells after 12 h, and causes cell death at 24 h in AC1-M88 cells. IC261 (1 μM) also induces apoptosis in the extravillous trophoblast hybrid cells. IC261 (1.25 μM) suppresses the proliferation of several pancreatic tumour cell lines, including ASPC-1, BxPc3, Capan-1, Colo357, MiaPaCa-2, Panc1, Panc89, PancTu-1 and PancTu-2 cells. IC261 (1.25 μM) specifically enhances CD95-mediated apoptosis of pancreatic tumour cells.(In Vivo):IC261 (20.5 mg/kg) inhibits tumor growth of PancTu-2 cells in SCID mice, downregulates several anti-apoptotic proteins, such as CK1δ/ , KRAS, and IL6 and upregulates p21, ATM, CHEK1 and STAT1 in mice.