(DSS)6-AZD8329

`(DSS)6-AZD8329` is an osteoblast-specific, bone-targeted peptide-drug conjugate (PDC) designed to selectively inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in bone tissue. Developed by researchers at Hong Kong Baptist University, the conjugate consists of the selective 11β-HSD1 inhibitor AZD8329 covalently linked to a bone-targeting peptide, (DSS)6 (six repeating aspartate-serine-serine sequences), which has a high affinity for hydroxyapatite on bone-forming surfaces. By selectively blocking 11β-HSD1 in osteoblasts, (DSS)6-AZD8329 prevents local glucocorticoid overactivation and restores Egr2-governed osteogenic activity and glucose uptake. In preclinical models of high-fat diet (HFD)-induced obesity, intravenous administration of (DSS)6-AZD8329 significantly promotes bone formation, improves skeletal glucose handling, and ameliorates systemic metabolic dysregulation, including obesity and glucose intolerance, without causing the systemic side effects or HPA axis activation associated with non-targeted 11β-HSD1 inhibitors.

Other names

bone-targeted 11beta-HSD1 inhibitorbone-targeted11beta-HSD1 inhibitorbone-targeted-11beta-HSD1 inhibitorbone-targeted 11β-HSD1 inhibitorosteoblast-specific 11beta-HSD1 inhibitorosteoblast-specific11beta-HSD1 inhibitorosteoblast-specific-11beta-HSD1 inhibitorosteoblast-specific 11β-HSD1 inhibitor