A new class of SHIP1 agonists that offer the potential for the development of new treatments for a variety of diseases.
Background: An agonist is a drug or substance that binds to a cell receptor, producing the same action as the substance that would naturally bind to the receptor. Agonists form the basis for a wide variety of therapeutics. The SH-2 containing inositol 5’ polyphosphatase 1 (SHIP1) is a multifunctional protein expressed predominantly by hematopoietic cells. Over the last decade, SHIP1 has been identified as a therapeutic target due to its role in immune cells. It also plays a role in the survival of certain cancers. For example, a SHIP1-selective inhibitor has been shown to be an effective promoter of immune responses to tumor cells, a chemotherapeutic for Blymphoid cancers, hematopoietic stem cell (HSC) mobilization, and engraftment of autologous and allogeneic HSC in murine models of disease or transplantation.
Technology Overview: This technology consists of analogs to K306, the most potent SHIP1 agonist identified to date. K306 exhibits selectivity for SHIP1 vs. the paralog enzyme SHIP2; this activation does not require the C2 domain of SHIP1 (which other known SHIP1 agonists require). Thus, K306 represents a new class of SHIP1 agonists with a novel mode of agonism. K306 can also suppress induction of inflammatory cytokines and iNOS in macrophages or microglia, but not by their SHIP1-deficient counterparts. In addition, K306 reduces TNF-α production in vivo in an LPS-induced endotoxemia assay. Finally, K306 enhances phagolysosomal degradation of synaptosomes and dead neurons by microglia, revealing a novel function for SHIP1 that might be exploited therapeutically in dementia.
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Advantages: • Represents a new class of SHIP1 agonists with a novel mode of agonism. • Suppresses induction of inflammatory cytokines and iNOS in macrophages or microglia. • Reduces TNF-α production in vivo in an LPS-induced endotoxemia assay. • Offers a potential treatment for dementia.
Applications: The primary application for this technology is the development of therapeutics based on SHIP1 agonists.
Intellectual Property Summary: Patent application filed on 11/15/22: 63/425,601
Stage of Development: TRL 3 - Experimental proof of concept
Licensing Status: This technology is available for licensing.
Licensing Potential: This technology would be of interest to anyone involved in medical research and development, including: • Pharmaceutical and healthcare companies. • Hospitals. • Universities. • Medical research laboratories.