采用生物信息学和化学信息学相结合的方法，开发非对称双价 AMPA 受体正变构调节剂作为神经保护剂。
A combined bioinformatics and chemoinformatics approach for developing asymmetric bivalent AMPA receptor positive allosteric modulators as neuroprotective agents.
机构信息
Chemical Biology Program, Department of Pharmacology & Toxicology, Center for Addiction Research, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
出版信息
ChemMedChem. 2013 Feb;8(2):226-30. doi: 10.1002/cmdc.201200554. Epub 2012 Dec 20.
Abstract
PAMs new in town! An effective, combined bioinformatics and chemoinformatics approach was applied to the design of novel asymmetric bivalent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor positive allosteric modulators (PAMs) with marked potency in vitro and efficacy in vivo for preventing neuroapoptosis. The novel chemotype could provide pharmacological probes and potential therapeutic agents for glutamatergic hypofunction and its related neurological and psychiatric disorders.
摘要
PAMs 新到小镇！采用有效的组合生物信息学和化学信息学方法，设计了新型不对称双价 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体正变构调节剂（PAMs），该调节剂具有显著的体外活性和体内预防神经细胞凋亡的功效。这种新型化学结构类型可为谷氨酸能功能低下及其相关神经和精神疾病提供药理学探针和潜在的治疗剂。
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本文引用的文献
1
5-Arylbenzothiadiazine Type Compounds as Positive Allosteric Modulators of AMPA/Kainate Receptors.5-芳基苯并噻二嗪类化合物作为AMPA/海人酸受体的正变构调节剂
ACS Med Chem Lett. 2011 Nov 14;3(1):25-9. doi: 10.1021/ml200184w. eCollection 2012 Jan 12.
2
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.
3
Defining desirable central nervous system drug space through the alignment of molecular properties, in vitro ADME, and safety attributes.通过分子特性、体外 ADME 和安全性特征的一致性来定义理想的中枢神经系统药物空间。
ACS Chem Neurosci. 2010 Jun 16;1(6):420-34. doi: 10.1021/cn100007x. Epub 2010 Mar 25.
4
Finding the sweet spot: the role of nature and nurture in medicinal chemistry.寻找最佳平衡点：自然与培育在药物化学中的作用。
Nat Rev Drug Discov. 2012 Apr 30;11(5):355-65. doi: 10.1038/nrd3701.
5
The Protein Data Bank at 40: reflecting on the past to prepare for the future.蛋白质数据库 40 年：回顾过去，展望未来。
Structure. 2012 Mar 7;20(3):391-6. doi: 10.1016/j.str.2012.01.010.
6
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Mol Pharmacol. 2011 Aug;80(2):267-80. doi: 10.1124/mol.110.070243. Epub 2011 May 4.
7
Probing the links between in vitro potency, ADMET and physicochemical parameters.探究体外效力、ADMET 和理化参数之间的联系。
Nat Rev Drug Discov. 2011 Mar;10(3):197-208. doi: 10.1038/nrd3367.
8
Integration of lead optimization with crystallography for a membrane-bound ion channel target: discovery of a new class of AMPA receptor positive allosteric modulators.将先导优化与晶体学相结合用于膜结合离子通道靶标：发现新型 AMPA 受体正变构调节剂。
J Med Chem. 2011 Jan 13;54(1):78-94. doi: 10.1021/jm100679e. Epub 2010 Dec 3.
9
Positive allosteric modulators of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的正变构调节剂
J Med Chem. 2010 Oct 28;53(20):7271-9. doi: 10.1021/jm1000419.
10
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Curr Med Chem. 2010;17(30):3503-13. doi: 10.2174/092986710792927840.
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