Small Molecule Dysregulation of TEAD Lipidation Induces a Dominant-Negative Inhibition of Hippo Pathway Signaling was written by Holden, Jeffrey K.;Crawford, James J.;Noland, Cameron L.;Schmidt, Stephen;Zbieg, Jason R.;Lacap, Jennifer A.;Zang, Richard;Miller, Gregory M.;Zhang, Yue;Beroza, Paul;Reja, Rohit;Lee, Wendy;Tom, Jeffrey Y. K.;Fong, Rina;Steffek, Micah;Clausen, Saundra;Hagenbeek, Thjis J.;Hu, Taishan;Zhou, Zheng;Shen, Hong C.;Cunningham, Christian N.. And the article was included in Cell Reports in 2020.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine This article mentions the following:
The transcriptional enhanced associate domain (TEAD) family of transcription factors serves as the receptors for the downstream effectors of the Hippo pathway, YAP and TAZ, to upregulate the expression of multiple genes involved in cellular proliferation and survival. Recent work identified TEAD S-palmitoylation as critical for protein stability and activity as the lipid tail extends into a hydrophobic core of the protein. Here, we report the identification and characterization of a potent small mol. that binds the TEAD lipid pocket (LP) and disrupts TEAD S-palmitoylation. Using a variety of biochem., structural, and cellular methods, we uncover that TEAD S-palmitoylation functions as a TEAD homeostatic protein level checkpoint and that dysregulation of this lipidation affects TEAD transcriptional activity in a dominant-neg. manner. Furthermore, we demonstrate that targeting the TEAD LP is a promising therapeutic strategy for modulating the Hippo pathway, showing tumor stasis in a mouse xenograft model. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Quality Control of 1H-Benzo[d][1,2,3]triazol-1-amine
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics