美科学家研发首个能突破“血脑屏障”的研发药HIV新药

在推进清除大脑中使艾滋病无法治愈的感染的过程中，为了克服这一障碍并消除艾滋病毒的血脑屏障最后据点，因为艾滋病毒可以穿过血脑屏障，美科而使大脑成为艾滋病毒的学家V新储存库。

他们在《Journal of the American Chemical Society》上所描述的进展是允许药物跨越所谓的“血脑屏障”（BBB）并治疗脑部疾病。

在推进清除大脑中使艾滋病无法治愈的感染的过程中，

血脑屏障示意图

Jean Chmielewski, Christine Hrycyna以及同事们解释到，如抗癌和抗精神分裂症药物。

相关英文论文摘要：

Toward Eradicating HIV Reservoirs in the Brain: Inhibiting P-Glycoprotein at the Blood–Brain Barrier with Prodrug Abacavir Dimers

Eradication of HIV reservoirs in the brain necessitates penetration of antiviral agents across the blood–brain barrier (BBB), a process limited by drug efflux proteins such as P-glycoprotein (P-gp) at the membrane of brain capillary endothelial cells. We present an innovative chemical strategy toward the goal of therapeutic brain penetration of the P-gp substrate and antiviral agent abacavir, in conjunction with a traceless tether. Dimeric prodrugs of abacavir were designed to have two functions: inhibit P-gp efflux at the BBB and revert to monomeric therapeutic within cellular reducing environments. The prodrug dimers are potent P-gp inhibitors in cell culture and in a brain capillary model of the BBB. Significantly, these agents demonstrate anti-HIV activity in two T-cell-based HIV assays, a result that is linked to cellular reversion of the prodrug to abacavir. This strategy represents a platform technology that may be applied to other therapies with limited brain penetration due to P-glycoprotein.

英文原文链接：https://pubs.acs.org/doi/full/10.1021/ja206867t

作者承认美国国立卫生研究所和普渡大学研究基金会为该项研究提供了资金资助。

他们的做法涉及用“系绳”使两个抗HIV药物分子胶合在一起。

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