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bone-targeted gamma-secretase inhibitor
- Development stage
- Preclinical
- Lead developer
- BioVinc
- Modality
- Small Molecules
- Administration
- Intraperitoneal
01
Overview
Bone-targeted gamma-secretase inhibitor (BT-GSI) is a bone-targeted drug conjugate designed to localize Notch pathway inhibition to the bone and bone marrow microenvironment. Developed by BioVinc in collaboration with the University of Arkansas for Medical Sciences, BT-GSI consists of a modified, low-activity bisphosphonate moiety with high bone affinity conjugated to the small molecule gamma-secretase inhibitor XII (GSI-XII) via a pH-sensitive, acid-cleavable hydrazine linker. This design allows the conjugate to bind to bone hydroxyapatite and selectively release the active GSI-XII cargo in the acidic microenvironment of bone resorption sites. By targeting the bone niche, BT-GSI inhibits Notch signaling in multiple myeloma cells and osteoclasts, reducing tumor growth and preventing osteolytic bone destruction without inducing the severe gastrointestinal toxicity typically associated with systemic gamma-secretase inhibitors.
- Other names
- bisphosphonate-conjugated gamma-secretase inhibitorbisphosphonate-conjugated γ-secretase inhibitorbone-targeted Notch inhibitorGSI-XII-bisphosphonate conjugate
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