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Highly fluorescent and HDAC6 selective scriptaid analogues
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2018-11-09 , DOI: 10.1016/j.ejmech.2018.11.020
Cassandra L. Fleming , Anthony Natoli , Jeannette Schreuders , Mark Devlin , Prusothman Yoganantharajah , Yann Gibert , Kathryn G. Leslie , Elizabeth J. New , Trent D. Ashton , Frederick M. Pfeffer
中文翻译:
高荧光和HDAC6选择性脚本类似物
更新日期:2018-11-09
European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2018-11-09 , DOI: 10.1016/j.ejmech.2018.11.020
Cassandra L. Fleming , Anthony Natoli , Jeannette Schreuders , Mark Devlin , Prusothman Yoganantharajah , Yann Gibert , Kathryn G. Leslie , Elizabeth J. New , Trent D. Ashton , Frederick M. Pfeffer
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Fluorescent scriptaid analogues with excellent HDAC6 selectivity (HDAC1/6 > 500) and potency (HDAC6 IC50 < 5 nM) have been synthesised and evaluated. The highly fluorescent nature of the compounds (up to ΦF = 0.83 in DMSO and 0.38 in aqueous buffer) makes them ideally suited for cellular imaging and visualisation of their cytoplasmic localisation was readily accomplished. Whole organism imaging in zebrafish confirmed both the vascular localisation of the new inhibitors and the impact of HDAC6 inhibition on in vivo development.
中文翻译:

高荧光和HDAC6选择性脚本类似物
合成并评估了具有出色HDAC6选择性(HDAC1 / 6> 500)和效能(HDAC6 IC 50 <5 nM)的荧光脚本类似物。化合物的高荧光性质(最高Φ ˚F =在DMSO 0.83和在水性缓冲液中0.38)使得它们理想地适合于细胞成像以及它们的细胞质定位的可视化可以容易地完成。斑马鱼的全生物成像证实了新抑制剂的血管定位以及HDAC6抑制作用对体内发育的影响。