62230-10-8Relevant academic research and scientific papers
Development of Kinase-Selective, Harmine-Based DYRK1A Inhibitors that Induce Pancreatic Human β-Cell Proliferation
Kumar, Kunal,Wang, Peng,Sanchez, Roberto,Swartz, Ethan A,Stewart, Andrew F.,Devita, Robert J.
, p. 7687 - 7699 (2018)
DYRK1A has been implicated as an important drug target in various therapeutic areas, including neurological disorders and oncology. DYRK1A has more recently been shown to be involved in pathways regulating human β-cell proliferation, thus making it a potential therapeutic target for both Type 1 and Type 2 diabetes. Our group, using a high-throughput phenotypic screen, identified harmine that is able to induce β-cell proliferation both in vitro and in vivo. Since harmine has suboptimal kinase selectivity, we sought to expand structure-activity relationships for harmine's DYRK1A activity, to enhance selectivity, while retaining human β-cell proliferation capability. We carried out the optimization of the 1-position of harmine and synthesized 15 harmine analogues. Six compounds showed excellent DYRK1A inhibition with IC50 in the range of 49.5-264 nM. Two compounds, 2-2 and 2-8, exhibited excellent human β-cell proliferation at doses of 3-30 μM, and compound 2-2 showed improved kinase selectivity as compared to harmine.
KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE
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, (2019/10/15)
Described herein are compounds having the following structure: formula (I) or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof. Also disclosed are compositions containing the compounds, methods of inhibiting activity of DYRKl A in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.
New β-Carboline Alkaloids from a Chinese Medicinal Plant, Arenaria kansuensis. Structures of Arenarines A, B, C, and D
Wu, Feng-E,Koike, Kazuo,Nikaido, Tamotsu,Sakamoto, Yohko,Ohmoto, Taichi,Ikeda, Kejii
, p. 1808 - 1809 (2007/10/02)
Six β-carboline alkaloids were isolated from a Chinese medicinal plant, Arenaria kansuensis.The structures of four new alkaloids named arenarines A, B, C, and D were identified based on spectral and chemical evidence.Keywords - Arenaria kansuensis; arenarine A; arenarine B; arenarine C; arenarine D; Cariophyllaceae; β-carboline; alkaloid.
