Yeats inhibitors and methods of use thereof

US11512111B2 · kind B2 · utility

Assignee

• University of Hong Kong · CN

Inventors

• Xiang Li · Beijing, CN
• Xin Li · Shanghai, CN

Key dates

• Filing date: Nov 26, 2018
• Grant date: Nov 29, 2022
• Expiry date: Nov 26, 2038

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Disclosed herein are compositions and methods suitable for treating acute leukemia by inhibiting π π π stacking in the YEATS protein domain. YEATS protein domains are typically found in a variety of chromatin modification molecular complexes. Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Quantitative analysis of the inhibitory activity of YEATS domain inhibitors by use of a fluorescence-based assay revealed that several of the tested inhibitors achieved 50% inhibition at the submicro/nanomolar level. As such, provided is the use of small molecule inhibitors that target the ENL YEATS domain to selectively kill leukemic MLL-r cells.