Aquaporin-Targeted Therapeutics: State-of-the-Field.
Aquaporin-Targeted Therapeutics: State-of-the-Field.
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DOI：
10.1007/978-94-024-1057-0_16
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发表时间：
2017
影响因子：
--
通讯作者：
Verkman AS
中科院分区：
文献类型：
--
作者：
Tradtrantip L;Jin BJ;Yao X;Anderson MO;Verkman AS
以水通道蛋白为靶点的药物具有广泛的临床应用潜力，包括癌症、肥胖、水肿、青光眼、皮肤病等。星形胶质细胞水通道水通道蛋白-4是一个特别引人注目的靶标，因为它在脑水运动，神经兴奋和胶质细胞瘢痕形成中起作用，并且因为它是神经炎性脱髓鞘疾病视神经脊髓炎的病原性自身抗体的靶标。人们对水通道蛋白的小分子抑制剂的鉴定非常感兴趣，从已知离子运输抑制剂的测试中出现了各种候选物，以及化合物筛选和计算化学。然而，总的来说，报道的水通道蛋白抑制剂的活性并没有在重新测试中得到证实，这可能是由于在最初的鉴定研究中使用的水运分析中的技术问题，以及在调节小的、致密的、含孔的膜蛋白的活性方面的挑战。本文综述了水通道蛋白调节小分子和生物制剂领域的研究现状，以及未来发展面临的挑战和机遇。
Drugs targeting aquaporins have broad potential clinical applications, including cancer, obesity, edema, glaucoma, skin diseases and others. The astrocyte water channel aquaporin-4 is a particularly compelling target because of its role of brain water movement, neuroexcitation and glia scarring, and because it is the target of pathogenic autoantibodies in the neuroinflammatory demyelinating disease neuromyelitis optica. There has been considerable interest in the identification of small molecule inhibitors of aquaporins, with various candidates emerging from testing of known ion transport inhibitors, as well as compound screening and computational chemistry. However, in general, the activity of reported aquaporin inhibitors has not been confirmed on retesting, which may be due to technical problems in water transport assays used in the original identification studies, and the challenges in modulating the activity of small, compact, pore-containing membrane proteins. We review here the state of the field of aquaporin-modulating small molecules and biologics, and the challenges and opportunities in moving forward.
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DOI：
10.1085/jgp.201110712
发表时间：
2012-01
期刊：
The Journal of general physiology
影响因子：
--
作者：
Baumgart F;Rossi A;Verkman AS
通讯作者：
Verkman AS
影响因子：
82.9
作者：
Manley, GT;Fujimura, M;Verkman, AS
通讯作者：
Verkman, AS
影响因子：
3.4
作者：
Martins, Ana Paula;Ciancetta, Antonella;Casini, Angela
通讯作者：
Casini, Angela
DOI：
10.1073/pnas.1210662109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Baum, Bruce J.;Alevizos, Ilias;Illei, Gabor G.
通讯作者：
Illei, Gabor G.
影响因子：
3.5
作者：
Huber, Vincent J.;Tsujita, Mika;Nakada, Tsutomu
通讯作者：
Nakada, Tsutomu