BT-GSI

BT-GSI is a bone-targeted gamma-secretase inhibitor (GSI) designed to inhibit Notch signaling specifically within the bone marrow microenvironment. It consists of the GSI-XII molecule conjugated to a bone-targeting (BT) moiety with high bone affinity via an acid-hydrolyzable linker. This design allows the drug to remain inactive systemically and release the active GSI only under the acidic conditions found in the bone-tumor niche, such as those created by multiple myeloma (MM) cells and osteoclasts. By localizing Notch inhibition to the bone, BT-GSI aims to eliminate both proliferating and dormant MM cells and prevent osteolytic bone destruction while avoiding the dose-limiting gastrointestinal toxicity typically associated with systemic gamma-secretase inhibitors. Preclinical studies have demonstrated that BT-GSI can reduce tumor burden, induce apoptosis in dormant cancer cells, and preserve bone mass in models of established multiple myeloma.

Other names

bone-targeted Notch inhibitorbone-targeted gamma-secretase inhibitorGSI-XII conjugate