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bone-targeted GPAT inhibitor
- Development stage
- Preclinical
- Modality
- Peptide-Drug Conjugates → Peptide Conjugates → Peptides, Small Molecules
- Administration
- Intraperitoneal
01
Overview
The bone-targeted GPAT inhibitor (also known as bone-GPATi or FSG67-K(TMR)-(Asp)6-amide) is a bone-targeted small molecule-peptide conjugate developed by researchers at Massachusetts General Hospital and Harvard Medical School. It consists of the pan-glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67 conjugated to a bone-targeting poly-aspartic acid peptide (Asp6) and a tetramethylrhodamine (TMR) fluorophore for tracking. By selectively localizing to the mineralized bone matrix via hydroxyapatite binding and inhibiting GPAT (particularly GPAT2 in osteoblasts), the compound redirects osteoblast free fatty acid (FFA) metabolism away from lysophosphatidic acid (LPA) synthesis and toward mitochondrial fatty acid oxidation. This metabolic reprogramming restores skeletal mineralization, lowers circulating phosphate and fibroblast growth factor 23 (FGF23) levels, and attenuates vascular calcification and cardiac hypertrophy in models of chronic kidney disease (CKD).
- Other names
- FSG67-K(TMR)-(Asp)6-amidebone-targeted GPAT inhibitor
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