AI Article Synopsis
- BCATs are enzymes that initiate the breakdown of essential branched-chain amino acids, producing glutamate, and are important in various cancers.
- Researchers discovered a new class of BCAT1/2 inhibitors, called (trifluoromethyl)pyrimidinediones, through high-throughput screening and structural optimization with X-ray crystallography.
- The top candidate, BAY-069, shows strong cellular activity and excellent selectivity, and along with a control compound (BAY-771), was shared with the Structural Genomics Consortium for further research.
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9661481 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.2c00441 | DOI Listing |
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Article Synopsis
- BCATs are enzymes that initiate the breakdown of essential branched-chain amino acids, producing glutamate, and are important in various cancers.
- Researchers discovered a new class of BCAT1/2 inhibitors, called (trifluoromethyl)pyrimidinediones, through high-throughput screening and structural optimization with X-ray crystallography.
- The top candidate, BAY-069, shows strong cellular activity and excellent selectivity, and along with a control compound (BAY-771), was shared with the Structural Genomics Consortium for further research.
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