Apr 22, 2024 · In this study, we designed and synthesized a series of TEAD PROTACs by connecting a pan-TEAD inhibitor with the CRBN ligand thalidomide. A representative compound, 27, exhibited potent antiproliferative activity against NF2 -deficient NCI-H226 cells.

Sep 30, 2024 · We report the TEAD-targeting proteolysis targeting chimera (PROTAC), HC278, which achieves effective and specific targeting of TEAD1 and TEAD3 at low nanomolar doses while weakly degrading TEAD2 and TEAD4 at higher doses. Proteomic analysis of >6000 proteins confirmed their highly selective TEAD1 and TEAD3 degradation.

Jan 13, 2025 · In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders. Both series yielded potent TEAD degraders, including 19 and 40 (H122), which induced TEAD1 degradation with DC 50 < 10 nM.

Jun 5, 2023 · In this article, we report the discovery of a potent SMI that reversibly binds to all four human TEAD paralogs and allosterically blocks YAP/TAZ binding. We demonstrate that this molecule...

PROTAC TEAD degrader-1 selectively degrades the Flag TEAD2 in a ubiquitin proteasome-dependent manner, with a DC50 of 54.1 nM in 293T cells, inhibits proliferation of NF2-deficient NCI-H226 with an IC50 of 0.21 μM, and regulates expressions of …

May 18, 2021 · Here, we review current understanding of TF-mediated gene regulation, discuss successful targeting strategies and highlight ongoing challenges and emerging approaches to address them. DNA-binding...

Jun 28, 2018 · Transcriptional enhanced associate domain (TEAD) proteins are the downstream effectors of the Hippo signaling pathway that regulate cell proliferation and stem cell functions. TEADs are unable to activate transcription and require the help of coactivators such as YAP, TAZ, VgLL, and p160 proteins.

Jan 26, 2023 · Another exciting avenue to inhibit TEAD activity is to design a PROTAC (proteolysis targeting chimera) where TEADs can be proteolytically degraded through a TEAD- and E3-ligase-binding heterobifunctional ligand that couples TEAD to the degradation machinery.

Sep 19, 2023 · Proteolysis-Targeting Chimera (PROTAC) technology was employed to design and synthesize a series of YAP degraders. Here, our degraders were created by linking NSC682769, a previously reported YAP binder, with either VHL ligand 2 or pomalidomide using various linkers of different lengths and types.

Jan 13, 2025 · In this study, we report two series of TEAD PROTACs based on CRBN binders and VHL binders. Both series yielded potent TEAD degraders, including 19 and 40 (H122), which induced TEAD1 degradation with DC 50 < 10 nM.