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Review Article

临床试验中已建立和正在试验的GPCR家族：目标选择的回顾

卷 20, 期 5, 2019

页: [522 - 539] 页: 18

弟呕挨: 10.2174/1389450120666181105152439

价格: $65

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摘要

临床试验中最大的药物目标家族由gpcrs（G蛋白偶联受体）组成，约占FDA（食品和药物管理局）批准的108种独特gpcrs药物的34%。诸如结构中易于识别的保守基序、127个孤儿gpcrs（尽管采用了各种去孤技术）、用于验证药物靶点的定向功能抗体等因素拓宽了它们的治疗窗口。44个独特受体的晶体结构，未经探索的非嗅觉GPCRs（由50%的人类基因组编码）和205个配体-受体复合物的可用性现在为基于结构的发现和设计提供了强有力的基础。多药组学对精神分裂症、癌症等复杂疾病的影响越来越大，需要新的靶点，考虑到gpcrs的无歧视性和选择性，它们可以实现这一目的。同样，人类基因组内的自然遗传变异有时会迷惑某些药物的治疗预期，导致药物反应差异和不良药物反应。仅在美国，每年就有大约300亿美元因不良的不良反应而被抛售。为了抑制这些不良反应，对药物设计前景的认识，包括“偏离目标”的效果，减少了经济资源和时间，GPCRS家族在临床试验中已建立和当代的知识可以提供巨大的理解。阐述了gpcr蛋白家族的药物适应性及其在复杂疾病中的重要作用。甲级、B1级、C级和F级通常是一期（19%）、二期（29%）、三期（52%）研究中建立的家族和GPCR。从第一阶段的研究来看，在第二阶段的研究中，卷曲的受体占试验目标的最高，神经肽占第二阶段，黑素皮质素占第三阶段的研究。此外，还讨论了纳米化合物的生物应用，以及纳米药物和GPCR药物工业的未来前景。此外，还回顾了计算技术和用于不同目标验证的方法的使用，以及它们在基于GPCR的药物发现方面的未来潜力。

关键词: G蛋白偶联受体，药物靶点，临床试验，受体蛋白，药物发现和疾病。

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