Osteoadsorptive fluorogenic substrate of cathepsin k for imaging osteoclast activity and migration

US11219697B2 · kind B2 · utility

Assignees

• The Regents of the University of California · US
• University of Southern California · US

Inventors

• Ichiro Nishimura · Santa Monica, US
• Akishige Hokugo · Los Angeles, US
• Kenzo Morinaga · Los Angeles, US
• Charles E. McKenna · Santa Monica, US
• Boris A. Kashemirov · Los Angeles, US
• Eric Richard · Pasadena, US

Key dates

• Filing date: Jul 13, 2018
• Grant date: Jan 11, 2022
• Expiry date: Dec 22, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q1/37
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

In certain embodiments osteoadsorptive fluorogenic substrates of cathepsin K (or other proteases) are provided. Utilizing a bisphosphonate targeting moiety, the fluorogenic substrates provide effective bone-targeted protease sensor(s). In certain embodiments the “probes” comprise cleavable fluorophore-quencher pair linked by a cathepsin K (or other protease) peptide substrate and tethered to a bisphosphonate. Unlike existing probes that are cleared within a few days in vivo, the probes described herein (e.g., OFS-1) allow for monitoring resorption over the course of longer time periods with a single dose.