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Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging.糖原合酶激酶-3（GSK-3）靶向治疗与成像
Theranostics. 2016 Feb 17;6(4):571-93. doi: 10.7150/thno.14334. eCollection 2016.
2
Discovery of Isonicotinamides as Highly Selective, Brain Penetrable, and Orally Active Glycogen Synthase Kinase-3 Inhibitors.发现异烟酰胺作为高度选择性、可穿透血脑屏障且口服有效的糖原合酶激酶-3抑制剂。
J Med Chem. 2016 Feb 11;59(3):1041-51. doi: 10.1021/acs.jmedchem.5b01550. Epub 2016 Jan 22.
3
Tau in physiology and pathology.tau 在生理学和病理学中的作用。
Nat Rev Neurosci. 2016 Jan;17(1):5-21. doi: 10.1038/nrn.2015.1. Epub 2015 Dec 3.
4
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Bioorg Med Chem Lett. 2015 Aug 15;25(16):3230-3. doi: 10.1016/j.bmcl.2015.05.085. Epub 2015 Jun 3.
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ACS Med Chem Lett. 2015 Mar 10;6(5):548-52. doi: 10.1021/acsmedchemlett.5b00044. eCollection 2015 May 14.
6
GSK-3 modulates cellular responses to a broad spectrum of kinase inhibitors.GSK-3 调节细胞对广泛的激酶抑制剂的反应。
Nat Chem Biol. 2015 Jan;11(1):58-63. doi: 10.1038/nchembio.1690. Epub 2014 Nov 17.
7
Synthesis and evaluation of [(11)C]PyrATP-1, a novel radiotracer for PET imaging of glycogen synthase kinase-3β (GSK-3β).新型糖原合酶激酶-3β（GSK-3β）正电子发射断层显像（PET）放射性示踪剂[(11)C]PyrATP-1的合成与评价
Nucl Med Biol. 2014 Jul;41(6):507-12. doi: 10.1016/j.nucmedbio.2014.03.025. Epub 2014 Apr 2.
8
Alternative approaches for PET radiotracer development in Alzheimer's disease: imaging beyond plaque.阿尔茨海默病正电子发射断层显像（PET）放射性示踪剂开发的替代方法：超越斑块的成像
J Labelled Comp Radiopharm. 2014 Apr;57(4):323-31. doi: 10.1002/jlcr.3158. Epub 2013 Dec 11.
9
Lessons learnt from glycogen synthase kinase 3 inhibitors development for Alzheimer's disease.从阿尔茨海默病糖原合酶激酶 3 抑制剂的研发中吸取的经验教训。
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10
Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties.超越规则：中枢神经系统多参数优化 (CNS MPO) 方法的开发，以实现类似药物特性的一致性。
ACS Chem Neurosci. 2010 Jun 16;1(6):435-49. doi: 10.1021/cn100008c. Epub 2010 Mar 25.

发现一种高选择性糖原合酶激酶-3 抑制剂（PF-04802367），可调节大脑中的 Tau 磷酸化：用于 PET 神经影像学的翻译。

Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor (PF-04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging.

机构信息

Gordon Center for Medical Imaging & Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA, 02114, USA.

Pfizer Worldwide Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT, 06340, USA.

出版信息

Angew Chem Int Ed Engl. 2016 Aug 8;55(33):9601-5. doi: 10.1002/anie.201603797. Epub 2016 Jun 29.

DOI:10.1002/anie.201603797
PMID:27355874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4983481/
Abstract

Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF-367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A (11) C-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding.

摘要

糖原合酶激酶-3（GSK-3）在糖尿病、肿瘤学和神经学中调节多种细胞过程。N-(3-(1H-1,2,4-三唑-1-基)丙基)-5-(3-氯-4-甲氧基苯基)恶唑-4-甲酰胺（PF-04802367 或 PF-367）已被确定为一种高效抑制剂，是迄今为止最具选择性的 GSK-3 拮抗剂之一。其在体外和体内调节 tau 磷酸化方面的功效已得到证明。虽然 PF-367 在脑组织中的结合动力学太快，无法成为有效的治疗药物，但 PF-367 的药代动力学特征非常适合发现中枢神经系统中的 GSK-3 放射性药物。PF-367 的 (11)C-同位素类似物已被合成，非人类灵长类动物的初步 PET 成像研究证实，我们已经克服了成像 GSK-3 的两个主要障碍，即合理的脑通透性和可置换性结合。