Design, synthesis and biological evaluation of novel 4-phenylisoquinolinone BET bromodomain inhibitors

Add time:08/24/2019    Source:sciencedirect.com

The bromodomain and extra-terminal (BET) family of epigenetic proteins has attracted considerable attention in drug discovery given its involvement in regulating gene transcription. Screening a focused small molecule library based on the bromodomain pharmacophore resulted in the identification of 2-methylisoquinoline-1-one as a novel BET bromodomain-binding motif. Structure guided SAR exploration resulted in >10,000-fold potency improvement for the BRD4-BD1 bromodomain. Lead compounds exhibited excellent potencies in both biochemical and cellular assays in MYC-dependent cell lines. Compound 36 demonstrated good physicochemical properties and promising exposure levels in exploratory PK studies.

We also recommend Trading Suppliers and Manufacturers of 4-Amino-1-methylisoquinoline (cas 104704-41-8). Pls Click Website Link as below: cas 104704-41-8 suppliers

Prev:Exploration of 3-methylisoquinoline-4-carbonitriles as protein kinase A inhibitors of Plasmodium falciparum
Next:Solubility and mixing thermodynamic properties of levamisole hydrochloride in twelve pure solvents at various temperatures)