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多价值OncoFAP衍生物的分子进化,增强瘤吸收和延长瘤保留

Andrea Galbiati¹, Matilde Bocci¹, Silvia Gervasoni²

¹R&D Department, Philochem AG, CH-8112 Otelfingen, Switzerland.

Journal of medicinal chemistry

|July 30, 2024

概括

研究人员开发了新的紧型OncoFAP多元器件,对纤维细胞激活蛋白 (FAP) 有了增强的亲和力. 这些新的配体表明瘤保留率增加,改善了癌症放射治疗的疗效.

科学领域:

在瘤学瘤学.
放射化学放射化学是指辐射化学.
分子成像学分子成像学

背景情况:

纤维细胞激活蛋白 (FAP) 是许多上皮癌的关键生物标志物.
目前的FAP向放射性连体具有短的瘤半衰期,限制了治疗潜力.
长时间的瘤保留对于有效的FAP向放射性干疗法至关重要.

研究的目的:

开发新的紧型OncoFAP多元器件,以提高FAP亲和度.
为了提高治疗应用的瘤停留时间.
为了评估新的FAP配体的体外和体内性能.

主要方法:

紧型OncoFAP多元器件的设计和合成.
在多聚合物-FAP相互作用的in silico分析.
在体外亲和度测试 (IC50测定).
在携带瘤的小鼠体内生物分布研究.

主要成果:

开发了具有低皮科莫尔IC50s的多元仪,表明高FAP亲和力.
在体分析中发现了有利的结合口袋相互作用.
在体外,TriOncoFAP-DOTAGA表现出卓越的特征,在体内有优越的生物分布.

结论:

紧型OncoFAP多元器件提供增强的FAP亲和力和改善的瘤保留.
TriOncoFAP-DOTAGA是FAP向癌症治疗的一个有希望的候选者.
这些发现支持下一代FAP向放射治疗的发展.

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