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Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders

机译：用脑渗透剂P2X7拮抗剂靶向神经炎炎症作为神经精神疾病的新疗效

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摘要

Incremental human plasma exposure of the P2X7 antagonist JNJ-54175446 caused a dose dependent attenuation of P2X7 dependent ex-vivo IL-1β release (ex-vivo LPS primed, ex-vivo Bz-ATP as 2nd stimulus) from human subjects (left). The dose of 50 mg JNJ-54175446 produced central target engagement as assessed by displacing the P2X7 PET ligand, [18F]JNJ-64413739 (right)

机译：P2X7拮抗剂JNJ-54175446的增量人血浆暴露引起了从人受试者（左）的P2X7依赖性ex-vivo IL-1β释放（ex-Vivo LPS引发，前体内BZ-ATP作为第二刺激）的剂量依赖性衰减。 50mg JNJ-54175446的剂量产生了中央目标接合，通过置换P2X7 PET配体，[18F] JNJ-64413739（右）评估

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期刊名称 Neuropsychopharmacology
作者
Anindya Bhattacharya; Marc Ceusters;
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作者单位

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年(卷),期 2019(45),1
年度 2019
页码 234–235
总页数 2
原文格式 PDF
正文语种
中图分类神经科学;药学;精神病学;
关键词

机译：药理学;神经系统中的离子通道;

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专利

1. Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders [J] . Anindya Bhattacharya, Marc Ceusters Neuropsychopharmacology . 2020,第1期

机译：用脑渗透剂P2X7拮抗剂靶向神经炎症作为神经精神疾病的新疗效
2. A Selective and Brain Penetrant p38 alpha MAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction (vol 62, pg 5298, 2019) [J] . Roy Saktimayee M., Minasov George, Arancio Ottavio, Journal of Medicinal Chemistry . 2020,第15期

机译：一种选择性和脑渗透P38αMapk抑制剂候选神经系统和神经精神疾病，可衰减神经炎炎症和认知功能障碍（Vol 62，PG 5298,2019）
3. A Selective and Brain Penetrant p38 alpha MAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction [J] . Roy Saktimayee M., Minasov George, Arancio Ottavio, Journal of Medicinal Chemistry . 2019,第11期

机译：一种选择性和脑渗透P38αMapk抑制剂抑制神经系统和神经精神疾病的候选者，其衰减神经炎症和认知功能障碍
4. Design and development towards a commercial route to a P2X7 antagonist [C] . Dave Ennis Process Development Symposium . 2013

机译：对P2X7拮抗剂的商业路线的设计与开发
5. Development of G-quadruplex stabilizers as anticancer drug therapy and selective agonists of the human oxytocin receptor as a therapeutic tool for neuropsychiatric disorders. [D] . Sassano, Maria Florencia. 2009

机译：G-四链体稳定剂作为抗癌药物疗法的发展以及人类催产素受体的选择性激动剂作为神经精神疾病的治疗工具的发展。
6. Synthesis SAR and Pharmacological Characterizationof Brain Penetrant P2X7 Receptor Antagonists [O] . Brad M. Savall, *, Duncan Wu, 2015

机译：合成SAR和药理学表征渗透剂P2X7受体拮抗剂的合成
7. Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders [O] . Anindya Bhattacharya, Marc Ceusters 2019

机译：用脑渗透剂P2X7拮抗剂靶向神经炎炎症作为神经精神疾病的新疗效
8. Therapeutic Targeting of P2X7 after TBI. [R] . Kimbler, D. 2012

机译：TBI后p2X7的治疗靶向。

Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders

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