Designing Selective SIK2 Inhibitors for Dual Anti-Inflammatory and Pro-Repair Effect

Inflammatory bowel disease and other chronic inflammatory diseases remain challenging to treat, in part because durable benefit may require more than suppression of pro-inflammatory signaling alone. Emerging biology suggests that salt-inducible kinase 2 (SIK2) sits at a key node of innate immune activation and tissue repair, making it an attractive target for diseases such as ulcerative colitis. In this Flash Talk, Peter Tummino, President of Research & Development at Nimbus Therapeutics, will discuss the discovery of highly selective small-molecule SIK2 inhibitors and the rationale for pursuing selective rather than broader SIK inhibition. The presentation will highlight how structure-based drug design enabled the identification of small-molecule inhibitors with high selectivity over SIK1 and SIK3, a profile intended to preserve the therapeutic potential of SIK2 modulation while avoiding liabilities associated with other SIK isoforms. He will also review data from preclinical colitis models and human ex vivo systems showing that selective SIK2 inhibition suppresses pro-inflammatory signaling while increasing IL-10, a cytokine associated with tissue repair and mucosal healing. Together, these findings support a differentiated therapeutic hypothesis—that selective SIK2 inhibitors may deliver a dual anti-inflammatory and pro-repair effect in inflammatory and autoimmune diseases. 00:00 Welcome and Introduction 9:01 Molecule Search 12:19 Presentation 42:42 Q&A If your company doesn’t have a subscription yet, reach out here to inquire about access: https://drughunter.com/plans Recorded on April 23rd, 2026, as a Drug Hunter Flash Talk. Sign up to be notified of future sessions here: https://drughunter.com/flash-talk-ser... Sign up for our free newsletter here: https://drughunter.com/newsletter-sig...