An updated patent review of TEAD modulators (2022-present).

Abstract

Introduction: The Transcriptional Enhanced Associated Domain (TEAD) family has attracted increasing attention due to its crucial role in the Hippo signaling pathway, which regulates cell growth, division, survival, differentiation, and tissue homeostasis in multicellular organisms. Inhibition of TEADs with small molecules has been shown to be an effective strategy for the treatment of tumors, and several compounds have entered clinical trials as monotherapy and/or combination therapy.

Areas covered: Due to the explosion of patent disclosures on TEAD modulators (inhibitors or degraders) in the last two years, this review focuses on the published patent literature on small molecule inhibitors or degraders of TEAD and their applications from June 2022 to present（March 2025）, as a complementary update to the previous patent review (2018-2022).

Expert opinion: The reported TEAD modulators can be categorized into 4 types: non-covalent inhibitors, covalent inhibitors, protein-protein interaction inhibitors and degraders. Meanwhile, the combination therapy with TEAD inhibitors and other kinases or mutated gene inhibitors has shown promising therapeutic effects in patients with various types of cancer, which has greatly expanded the application field of TEAD inhibitors in disease treatment.