Progress with YAP/TAZ-TEAD inhibitors: a patent review (2018-present)

Introduction The Hippo pathway represents a new opportunity for the treatment of cancer. Overexpression of Yes-associated protein (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ) or TEAD has been demonstrated in cancers and YAP mediates resistance to cancer drugs. Since 2018, the potential of this pathway has been illustrated by numerous articles and patents and the first drugs entering in clinical trial phase 1. Areas covered This review is limited to published patent applications that have disclosed direct small-molecule inhibitors of the YAP/TAZ-TEAD interaction. Expert opinion The YAP/TAZ-TEAD transcriptional complex is a promising target for the treatment of cancer. Approximately 30 international patents (used database: Sci-finder, query: TEAD; documents: patents; period: from 2017-January 2022) that disclose TEAD transcriptional inhibitors have been filled since 2018. The mechanism of action is not always described in the patents, we can divide the drugs into three different categories: (i) external TEAD ligands; (ii) non-covalent TEAD ligands of the palmitate pocket; (iii) covalent TEAD ligands, which bind into the palmitate pocket. The first molecules in clinical trial phase 1 are non-covalent TEAD ligands. The selective TEAD ligand have also been patented, published and selectivity could be of great interest for personalized medicine.

Automated summary

The Hippo pathway presents a new opportunity for cancer treatment, with YAP/TAZ-TEAD transcriptional complex being a promising target. Since 2018, approximately 30 international patents regarding TEAD transcriptional inhibitors have been filed, with drugs categorized into external TEAD ligands, non-covalent TEAD ligands, and covalent TEAD ligands. The first molecules entering clinical trial phase 1 are non-covalent TEAD ligands.