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Blood：PIKfyve激酶抑制剂-阿匹莫德（apilimod）作为治疗B细胞非霍奇金淋巴瘤的鉴定

2017-01-25 MedSci MedSci原创

阿匹莫德细胞毒淋巴瘤
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近期，一项发表在Bloo杂志上的研究通过高通量筛选临床阶段药物鉴定出了阿匹莫德作为抗增殖化合物的作用。阿匹莫德对PIKfyve脂质激酶表现出精确的特异性，并且与正常细胞相比在B细胞非霍奇金淋巴瘤（B-NHL）中具有选择性细胞毒活性。体外试验中，阿匹莫德显示纳摩尔级的活性；体内研究证明具有单一药剂效力并且与批准的B-NHL药物具有协同作用。使用生物化学和基因减少的方法，以及激酶域突变赋予抵抗的发现，

近期，一项发表在Bloo杂志上的研究通过高通量筛选临床阶段药物鉴定出了阿匹莫德作为抗增殖化合物的作用。阿匹莫德对PIKfyve脂质激酶表现出精确的特异性，并且与正常细胞相比在B细胞非霍奇金淋巴瘤（B-NHL）中具有选择性细胞毒活性。


体外试验中，阿匹莫德显示纳摩尔级的活性；体内研究证明具有单一药剂效力并且与批准的B-NHL药物具有协同作用。

使用生物化学和基因减少的方法，以及激酶域突变赋予抵抗的发现，研究者们证明阿匹莫德介导的细胞毒性是由PIKfyve的抑制而驱动实现的。

此外，通过全基因组CRISPR筛选支持证明，溶酶体功能障碍是促成阿匹莫德细胞毒性的关键作用。

在筛选中，已经鉴定出TFEB（溶酶体生物发生的主转录调节子）和内体/溶酶体基因CLCN7、OSTM1和SNX10是阿匹莫德敏感性的重要决定因素。

这些发现表明使用阿匹莫德所具有的溶酶体内稳态的破坏作用是治疗B-NHL的新方法。

原始出处：
Gayle S, Landrette S, Beeharry N, et al. Identification of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin lymphoma. Blood. 2017 Jan 19. pii: blood-2016-09-736892.

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    2017-03-05 smartjoy

    #激酶抑制剂#

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    2017-07-07 jklm09

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    2017-01-27 xiaoyeshuang

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    2017-01-27 redcrab

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    2017-01-27 photoman

    #B细胞非霍奇金淋巴瘤#

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