Tocris Bioscience™ ARN 3236

ARN 3236 is a potent of salt-inducible kinase 2 (SIK2) inhibitor (IC50 values are <1 nM, 6.63 nM and 21.63 nM for SIK2, SIK3 and SIK1 respectively). ARN 3236 inhibits centrosome separation by uncoupling the centrosome from the nucleus. It also induces cell-cycle arrest and apoptosis by attenuating the AKT/survivin pathway. ARN 3236 inhibits growth and enhances Taxol (Cat. No. 1097) sensitivity in ovarian cancer cell lines in vitro and in vivo. In human myeloid cells, ARN 3236 blocks TNF and induces IL-10 upon LPS stimulation; it also reduces the production of IL-1β upon activation of TLR4 and TLR2 signaling. In depression models, ARN 3236 exhibits antidepressant-like effects via the hippocampal CRTC1-CREB-BDNF pathway. ARN 3236 penetrates the blood-brain barrier, and it is orally bioavailable.