A targeted library screen reveals a new inhibitor scaffold for protein kinase D was written by Tandon, Manuj;Wang, Lirong;Xu, Qi;Xie, Xiangqun;Wipf, Peter;Wang, Qiming Jane. And the article was included in PLoS One in 2012.Category: benzofurans This article mentions the following:
Protein kinase D (PKD) has emerged as a potential therapeutic target in multiple pathol. conditions, including cancer and heart diseases. Potent and selective small mol. inhibitors of PKD are valuable for dissecting PKD-mediated cellular signaling pathways and for therapeutic application. In this study, we evaluated a targeted library of 235 small organic kinase inhibitors for PKD1 inhibitory activity at a single concentration Twenty-eight PKD inhibitory chemotypes were identified and six exhibited excellent PKD1 selectivity. Five of the six lead structures share a common scaffold, with compound 139 being the most potent and selective for PKD vs PKC and CAMK. Compound 139 was an ATP-competitive PKD1 inhibitor with a low double-digit nanomolar potency and was also cell-active. Kinase profiling anal. identified this class of small mols. as pan-PKD inhibitors, confirmed their selectivity again PKC and CAMK, and demonstrated an overall favorable selectivity profile that could be further enhanced through structural modification. Furthermore, using a PKD homol. model based on similar protein kinase structures, docking modes for compound 139 were explored and compared to literature examples of PKD inhibition. Modeling of these compounds at the ATP-binding site of PKD was used to rationalize its high potency and provide the foundation for future further optimization. Accordingly, using biochem. screening of a small number of privileged scaffolds and computational modeling, we have identified a new core structure for highly potent PKD inhibition with promising selectivity against closely related kinases. These lead structures represent an excellent starting point for the further optimization and the design of selective and therapeutically effective small mol. inhibitors of PKD. In the experiment, the researchers used many compounds, for example, 7-Hydroxy-2,3,4,5-tetrahydro-1H-benzofuro[2,3-c]azepin-1-one (cas: 521937-07-5Category: benzofurans).
7-Hydroxy-2,3,4,5-tetrahydro-1H-benzofuro[2,3-c]azepin-1-one (cas: 521937-07-5) belongs to benzofurans derivatives. Benzofuran is a core structural unit found in many naturally occurring compounds with multidirectional biological activities. Benzofurans are stable towards alkali and readily polymerize on treatment with sulfuric acid, due to which they are useful for the preparation of low cost chemically relatively inert resins.Category: benzofurans
Referemce:
Benzofuran – Wikipedia,
Benzofuran | C8H6O – PubChem