Definition

An orally bioavailable small molecule inhibitor of the salt inducible kinases 2 (SIK2) and 3 (SIK3), with potential antineoplastic activity. Upon oral administration of SIK inhibitor GRN-300, this agent targets, binds to and blocks the activity of SIK2 and SIK3. This prevents SIK2/3-mediated signaling, blocks centrosome separation, and inhibits proliferation in SIK2/3-overexpressing tumor cells. GRN-300 may enhance tumor sensitivity to other chemotherapeutic agents. SIK2/3, serine/threonine centrosome kinase family members required for bipolar mitotic spindle formation, are overexpressed in a variety of tumor cell types.