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开发一种新型治疗性抑制剂，可抑制脑内促炎细胞因子上调，减轻突触功能障碍和行为缺陷。

Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits.

作者信息

Hu Wenhui, Ralay Ranaivo Hantamalala, Roy Saktimayee M, Behanna Heather A, Wing Laura K, Munoz Lenka, Guo Ling, Van Eldik Linda J, Watterson D Martin

机构信息

Center for Drug Discovery and Chemical Biology, Northwestern University, 303 E. Chicago Avenue, Mail Code W896, Chicago, IL 60611, USA.

出版信息

Bioorg Med Chem Lett. 2007 Jan 15;17(2):414-8. doi: 10.1016/j.bmcl.2006.10.028. Epub 2006 Oct 17.

DOI:10.1016/j.bmcl.2006.10.028
PMID:17079143
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1868432/
Abstract

We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

摘要

我们报告了一种新型的、水溶性的、安全的小分子实验性治疗药物的研发情况，该药物可抑制脑损伤诱导的促炎细胞因子增加，从而减轻突触蛋白生物标志物的损失，并改善海马体依赖性行为缺陷。文中还介绍了活性药物成分化合物17的GMP生产方案。这种新型化合物的研发及其大规模可得性，为探索治疗中枢神经系统疾病的新的、可能具有疾病修饰作用的治疗方法提供了可能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/48025f1a0dcc/nihms16750f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/7336dea4a7bc/nihms16750f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/d4d1c7cb1ae8/nihms16750f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/48025f1a0dcc/nihms16750f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/7336dea4a7bc/nihms16750f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/d4d1c7cb1ae8/nihms16750f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a6/1868432/48025f1a0dcc/nihms16750f3.jpg

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本文引用的文献

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Nat Med. 2006 Sep;12(9):1005-15. doi: 10.1038/nm1484.
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TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study.肿瘤坏死因子-α调节治疗阿尔茨海默病：一项为期6个月的试点研究。
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Tumor necrosis factor inhibitors for rheumatoid arthritis.用于类风湿关节炎的肿瘤坏死因子抑制剂
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De novo and molecular target-independent discovery of orally bioavailable lead compounds for neurological disorders.用于神经系统疾病的口服生物可利用先导化合物的从头发现及分子靶点非依赖性发现
Curr Alzheimer Res. 2006 Jul;3(3):205-14. doi: 10.2174/156720506777632844.
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Drug discovery: selecting the optimal approach.药物研发：选择最佳方法。
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