Tian Lu

TL;DR: DC-TEADin02 was identified as the most potent, selective, covalent TEAD autopalmitoylation inhibitor with the IC50 value of 197 ± 19 nM while it showed minimal effect on TEAD-YAP interaction, and proved the validity of modulating transcriptional output in the Hippo signaling pathway through irreversible chemical interventions of TEADs autopalMIToylation activity.

TL;DR: Although many small molecule BRD 4 inhibitors with high potency and diverse scaffolds have been developed, the selectivity of most BRD4 inhibitors still needs to be improved, so the development of more selective small molecule inhibitors or combined use of drugs such as immunotherapy may provide new ideas for drug development.

TL;DR: The discovery of a potent and selective BET BD2 inhibitor BY27 (47) is reported, which shows that the triazole group of 47, water molecules, H433 and N429 in BRD2 BD2 established a water-bridged H-bonding network, which is responsible for the observed selectivities.

TL;DR: An AlphaScreen HTS system for the discovery of SMARCA2-BRD inhibitors was developed and the physicochemical conditions including pH, salt concentrations and detergent levels were optimized and DCSM06-05 may be used as a starting point for further medicinal chemistry optimization and could function as a chemical tool for SMAR CA2-related functional studies.

TL;DR: In this study, identification of a 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and subsequent incorporation of fragment 47 to the scaffold of ABBV-075 enabled the generation of a series of highly potent BET b romodomain inhibitors.