Design and synthesis of ()-3-benzylideneindolin-2-one derivatives as potential allosteric inhibitors of Aurora A kinase.

The mitotic kinase Aurora A, a pivotal regulator of the cell cycle, is overexpressed in various cancers and has emerged as one of the most promising targets for anticancer drug discovery. However, the lack of specificity and potential toxicity have impeded clinical trials involving orthosteric inhibitors. In this study, allosteric sites of Aurora A were predicted using the AlloReverse web server.

ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.

Sunlight perception and outdoor thermal comfort in college campuses: a new perspective.

The thermal comfort of outdoor spaces in colleges and universities is crucial for promoting outdoor activities and relieving psychological pressure. To evaluate outdoor thermal comfort from a new perspective, this study investigated subjects' sunlight perception through physical measurements and questionnaires. Sunlight perception was delineated through a combination of subjective assessments and objective measurements.

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells.

SIRT6 belongs to the conserved NAD-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD.

MDL-800, an allosteric activator of SIRT6, suppresses proliferation and enhances EGFR-TKIs therapy in non-small cell lung cancer.

Sirtuin 6 (SIRT6), a member of the sirtuin family, is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase that is involved in various physiological and pathological processes. SIRT6 is generally downregulated and linked to tumorigenesis in non-small cell lung carcinoma (NSCLC), thus regarded as a promising therapeutic target of NSCLC. In this study, we investigated whether MDL-800, an allosteric activator of SIRT6, exerted antiproliferation effect against NSCLC cells in vitro and in vivo.