Glutaminase inhibitor discovery and nanoparticle-enhanced delivery for cancer therapy

US10660861B2 · kind B2 · utility

Assignee

• THE JOHNS HOPKINS UNIVERSITY · US

Inventors

• Justin Hanes · Baltimore, US
• Barbara Slusher · Kingsville, US
• Anne Le · Baltimore, US
• Jie Fu · Beijing, CN
• Qingguo Xu · Glen Allen, US

Key dates

• Filing date: Jul 8, 2015
• Grant date: May 26, 2020
• Expiry date: Nov 1, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D417/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Currently available glutaminase inhibitors are generally poorly soluble, metabolically unstable, and/or require high doses, which together reduce their efficacy and therapeutic index. These can be formulated into nanoparticles and delivered safely and effectively for treatment of pancreatic cancer and other glutamine addicted cancers. Studies demonstrate that nanoparticle delivery of BPTES, relative to use of BPTES alone, can be safely administered and provides dramatically improved tumor drug exposure, resulting in greater efficacy. GLS inhibitors can be administered in higher concentrations with sub-100 nm nanoparticles, since the nanoparticles package the drug into “soluble” colloidal nanoparticles, and the nanoparticles deliver higher drug exposure selectively to the tumors due to the enhanced permeability and retention (EPR) effect. These factors result in sustained drug levels above the IC50 within the tumors for days, providing significantly enhanced efficacy compared to unencapsulated drug.