Fused in sarcoma (FUS) nuclear translocation inhibitors for preventing fibrosis

US12060396B2 · kind B2 · utility

Assignees

• VANDERBILT UNIVERSITY · US
• THE UNITED STATES AS REPRESENTED BY THE DEPARTMENT OF VETERANS AFFAIRS · US

Inventors

• Ambra A. POZZI · Nashville, US
• Manuel CHIUSA · Nashville, US
• Jack J. Hawiger · Sharon, US
• Jozef Zienkiewicz · Nashville, US

Key dates

• Filing date: Jan 29, 2018
• Grant date: Aug 13, 2024
• Expiry date: Jan 29, 2038

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed herein are compositions and methods for inhibiting collagen production mediated by the Fused in Sarcoma (FUS) ribonucleoprotein. As disclosed herein, the C terminal domain of FUS contains an uncommon nuclear localization sequence (NLS) motif called PY-NLS that binds the nuclear import receptor transportin. Phosphorylation of FUS leads to its association with transportin and nuclear translocation with consequent increased in collagen production. Therefore, disclosed herein is an isolated peptide having a transportin-binding moiety, which inhibits FUS from binding transportin, linked to a membrane translocating motif. These compositions and methods can be used to inhibit FUS-mediated collagen production, and treat fibrotic disease involving FUS-mediated collagen accumulation in kidneys and other organs displaying fibrotic diseases.