Probes for in vivo targeting of active cysteine proteases

US8343458B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Matthew S. Bogyo · Redwood City, US
• Galia Blum · Jerusalem, IL
• Alicia Berger · San Francisco, US
• Zhen Cheng · 红钢城街道, CN
• Sanjiv S. Gambhir · Portola Valley, US

Key dates

• Filing date: Apr 3, 2009
• Grant date: Jan 1, 2013
• Expiry date: Sep 17, 2030

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61B6/508
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Activity-based probes, which are specific for certain active cysteine proteases (caspase, cathepsin and legumain) and carry radioactive labels, are disclosed. The present probes comprise an acyloxymethyketone (AOMK) “warhead” that binds only to active enzyme. The probes further comprise peptide-like structure that targets the probe to a specific cysteine protease or protease family, and a radiolabel on the probe, which is bound to the targeted enzyme. It has been found that the present probes are stable in vivo and give specific target images distinguishable over background. The preferred probes are labeled with a positron-emitting agent such as 64Cu, 125I (SPECT) and 99mTc (PET). The probes show in vivo half-life and stability well suited for imaging.