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Publication Abstract from PubMed

The serine/threonine kinase DYRK1A has been implicated in regulation of a variety of cellular processes associated with cancer progression, including cell cycle control, DNA damage repair, protection from apoptosis, cell differentiation, and metastasis. In addition, elevated-level DYRK1A activity has been associated with increased severity of symptoms in Down's syndrome. A selective inhibitor of DYRK1A could therefore be of therapeutic benefit. We have used fragment and structure-based discovery methods to identify a highly selective, well-tolerated, brain-penetrant DYRK1A inhibitor which showed in vivo activity in a tumor model. The inhibitor provides a useful tool compound for further exploration of the effect of DYRK1A inhibition in models of disease.

Fragment-Derived Selective Inhibitors of Dual-Specificity Kinases DYRK1A and DYRK1B.,Lee Walmsley D, Murray JB, Dokurno P, Massey AJ, Benwell K, Fiumana A, Foloppe N, Ray S, Smith J, Surgenor AE, Edmonds T, Demarles D, Burbridge M, Cruzalegui F, Kotschy A, Hubbard RE J Med Chem. 2021 Jun 18. doi: 10.1021/acs.jmedchem.1c00024. PMID:34143631^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.