Pharmacology of Modulators of Alternative Splicing.
Pharmacology of Modulators of Alternative Splicing.
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DOI：
10.1124/pr.115.011239
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发表时间：
2017-01
影响因子：
21.1
通讯作者：
Donaldson LF
中科院分区：
文献类型：
--
作者：
Bates DO;Morris JC;Oltean S;Donaldson LF
人类基因组中超过95%的基因被选择性剪接以形成多个转录物，通常编码具有不同或相反功能的蛋白质。选择性剪接的控制现在正在阐明，并与此来的机会，开发的选择性剪接，可以控制细胞功能的调节剂。已经采取了许多方法来开发可以在实验上，有时在临床上影响剪接控制的化合物，从而产生潜在的新疗法。在这里，我们开发的概念，靶向选择性剪接可以导致相对特定的途径抑制剂/激活剂，导致抑制生理或病理过程，从肌肉生理学的变化，改变血管生成或疼痛。一些目前的选择性剪接的抑制剂/激活剂的目标和药理学证明和未来的方向进行了讨论。
More than 95% of genes in the human genome are alternatively spliced to form multiple transcripts, often encoding proteins with differing or opposing function. The control of alternative splicing is now being elucidated, and with this comes the opportunity to develop modulators of alternative splicing that can control cellular function. A number of approaches have been taken to develop compounds that can experimentally, and sometimes clinically, affect splicing control, resulting in potential novel therapeutics. Here we develop the concepts that targeting alternative splicing can result in relatively specific pathway inhibitors/activators that result in dampening down of physiologic or pathologic processes, from changes in muscle physiology to altering angiogenesis or pain. The targets and pharmacology of some of the current inhibitors/activators of alternative splicing are demonstrated and future directions discussed.