Deubiquitinase-targeting chimeras for targeted protein stabilization was written by Henning, Nathaniel J.;Boike, Lydia;Spradlin, Jessica N.;Ward, Carl C.;Liu, Gang;Zhang, Erika;Belcher, Bridget P.;Brittain, Scott M.;Hesse, Matthew J.;Dovala, Dustin;McGregor, Lynn M.;Valdez Misiolek, Rachel;Plasschaert, Lindsey W.;Rowlands, David J.;Wang, Feng;Frank, Andreas O.;Fuller, Daniel;Estes, Abigail R.;Randal, Katelyn L.;Panidapu, Anoohya;McKenna, Jeffrey M.;Tallarico, John A.;Schirle, Markus;Nomura, Daniel K.. And the article was included in Nature Chemical Biology in 2022.Category: imidazoles-derivatives This article mentions the following:
Many diseases are driven by proteins that are aberrantly ubiquitinated and degraded. These diseases would be therapeutically benefited by targeted protein stabilization (TPS). Here we present deubiquitinase-targeting chimeras (DUBTACs), heterobifunctional small mols. consisting of a deubiquitinase recruiter linked to a protein-targeting ligand, to stabilize the levels of specific proteins degraded in a ubiquitin-dependent manner. Using chemoproteomic approaches, we discovered the covalent ligand EN523 that targets a non-catalytic allosteric cysteine C23 in the K48-ubiquitin-specific deubiquitinase OTUB1. We showed that a DUBTAC consisting of our EN523 OTUB1 recruiter linked to lumacaftor, a drug used to treat cystic fibrosis that binds ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR), robustly stabilized ΔF508-CFTR protein levels, leading to improved chloride channel conductance in human cystic fibrosis bronchial epithelial cells. We also demonstrated stabilization of the tumor suppressor kinase WEE1 in hepatoma cells. Our study showcases covalent chemoproteomic approaches to develop new induced proximity-based therapeutic modalities and introduces the DUBTAC platform for TPS. [graphic not available: see fulltext] In the experiment, the researchers used many compounds, for example, 4-Bromo-1-methylimidazole (cas: 25676-75-9Category: imidazoles-derivatives).
4-Bromo-1-methylimidazole (cas: 25676-75-9) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.Category: imidazoles-derivatives
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem