小分子p300/连环蛋白拮抗剂可增强辐射后造血功能的恢复。
Small molecule p300/catenin antagonist enhances hematopoietic recovery after radiation.
作者信息
Zhao Yi, Wu Kaijin, Nguyen Cu, Smbatyan Goar, Melendez Elisabeth, Higuchi Yusuke, Chen Yibu, Kahn Michael
机构信息
Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California, United States of America.
Center for Molecular Pathways and Drug Discovery, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
出版信息
PLoS One. 2017 May 9;12(5):e0177245. doi: 10.1371/journal.pone.0177245. eCollection 2017.
There is currently no FDA approved therapeutic agent for ARS mitigation post radiation exposure. Here we report that the small molecule YH250, which specifically antagonizes p300/catenin interaction, stimulates hematopoiesis in lethally or sublethally irradiated mice. A single administration of YH250 24 hours post irradiation can significantly stimulate HSC proliferation, improve survival and accelerate peripheral blood count recovery. Our studies suggest that promotion of the expansion of the remaining HSC population via stimulation of symmetric non-differentiative proliferation is at least part of the mechanism of action.
目前尚无美国食品药品监督管理局（FDA）批准的用于减轻辐射暴露后急性放射综合征（ARS）的治疗药物。在此，我们报告小分子YH250可特异性拮抗p300/连环蛋白相互作用，在致死剂量或亚致死剂量照射的小鼠中刺激造血作用。照射后24小时单次给予YH250可显著刺激造血干细胞（HSC）增殖，提高生存率并加速外周血细胞计数恢复。我们的研究表明，通过刺激对称性非分化增殖来促进剩余HSC群体的扩增至少是其作用机制的一部分。
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