BAY-069, a Novel (Trifluoromethyl)pyrimidinedione-Based BCAT1/2 Inhibitor and Chemical Probe

[Image: see text] The branched-chain amino acid transaminases (BCATs) are enzymes that catalyze the first reaction of catabolism of the essential branched-chain amino acids to branched-chain keto acids to form glutamate. They are known to play a key role in different cancer types. Here, we report a...

Descripción completa

Detalles Bibliográficos
Autores principales: Günther, Judith, Hillig, Roman C., Zimmermann, Katja, Kaulfuss, Stefan, Lemos, Clara, Nguyen, Duy, Rehwinkel, Hartmut, Habgood, Matthew, Lechner, Christian, Neuhaus, Roland, Ganzer, Ursula, Drewes, Mark, Chai, Jijie, Bouché, Léa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9661481/
https://www.ncbi.nlm.nih.gov/pubmed/36261130
http://dx.doi.org/10.1021/acs.jmedchem.2c00441
Descripción
Sumario:[Image: see text] The branched-chain amino acid transaminases (BCATs) are enzymes that catalyze the first reaction of catabolism of the essential branched-chain amino acids to branched-chain keto acids to form glutamate. They are known to play a key role in different cancer types. Here, we report a new structural class of BCAT1/2 inhibitors, (trifluoromethyl)pyrimidinediones, identified by a high-throughput screening campaign and subsequent optimization guided by a series of X-ray crystal structures. Our potent dual BCAT1/2 inhibitor BAY-069 displays high cellular activity and very good selectivity. Along with a negative control (BAY-771), BAY-069 was donated as a chemical probe to the Structural Genomics Consortium.

Ejemplares similares