伪自然产品用于化学生物学和药物发现
Luca C Greiner1, Axel Pahl1, A Lina Heinzke2
1Max-Planck Institute of Molecular Physiology, Department of Chemical Biology, Otto-Hahn-Strasse 11, Dortmund 44227, Germany.
Journal of medicinal chemistry
|July 1, 2025
概括
伪天然产品 (PNP) 结合了天然产品 (NP) 碎片,用于更广泛的化学勘探. 分析表明PNP在药物发现和临床开发中越来越普遍,提供了新的机会.
科学领域:
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
- 计算化学计算化学
背景情况:
- 自然产品 (NPs) 是生物活性化合物发现的重要灵感来源.
- 伪自然产品 (PNP) 概念融合了NP碎片,通过基于碎片的设计探索更广泛的化学空间,保持生物相关性.
- PNP提供了一种战略,以导航化学多样性,同时利用自然产品支架的证明成功.
研究的目的:
- 描述PNP设计和发现的原则.
- 识别和描述具有新生物活性的PNP.
- 评估PNP在药物发现和临床开发中的流行率和趋势.
主要方法:
- 基于碎片的设计原则应用于NP结构.
- 对大型化学数据库 (ChEMBL 32,选库,临床化合物,批准药物) 的化学信息分析.
- 在临床与非临床化合物和随着时间的推移中对PNP发生的统计分析.
主要成果:
- 大约三分之一的历史开发的生物活性化合物和当前选化合物是PNP.
- 在药物发现管道和临床试验中,PNP的代表越来越多.
- 在临床化合物中,PNP的发生率比非临床化合物高54%,最近67%的临床化合物是PNP.
- 一组有限的176个NP片段组成了63%最近临床化合物的核心支架.
结论:
- PNPs代表着正在开发中的生物活性化合物的显著和不断增长的比例.
- PNP方法有效地扩大了化学空间,同时保持了与生物相关结构的联系.
- 对于未来的药物发现工作,PNP提供了大量的,未被充分探索的机会.
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