Allegretti, Paul A. published the artcileGeneration of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization, Recommanded Product: (6-Hydroxypyridin-3-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry (2020), 28(1), 115193, database is CAplus and MEDLINE.
Small mol. stimulation of β-cell regeneration has emerged as a promising therapeutic strategy for diabetes. Although chem. inhibition of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is sufficient to enhance β-cell replication, current lead compounds have inadequate cellular potency for in vivo application. Herein, we report the clin. stage anti-cancer kinase inhibitor OTS167 as a structurally novel, remarkably potent DYRK1A inhibitor and inducer of human β-cell replication. Unfortunately, OTS167’s target promiscuity and cytotoxicity curtails utility. To tailor kinase selectivity towards DYRK1A and reduce cytotoxicity we designed a library of fifty-one OTS167 derivatives based upon a modeled structure of the DYRK1A-OTS167 complex. Indeed, derivative characterization yielded several leads with exceptional DYRK1A inhibition and human β-cell replication promoting potencies but substantially reduced cytotoxicity. These compounds are the most potent human β-cell replication-promoting compounds yet described and exemplify the potential to purposefully leverage off-target activities of advanced stage compounds for a desired application.
Bioorganic & Medicinal Chemistry published new progress about 903899-13-8. 903899-13-8 belongs to pyridine-derivatives, auxiliary class Pyridine,Boronic acid and ester,Alcohol,Boronic Acids,Boronic acid and ester, name is (6-Hydroxypyridin-3-yl)boronic acid, and the molecular formula is C5H6BNO3, Recommanded Product: (6-Hydroxypyridin-3-yl)boronic acid.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem