PO.CH01.02 · 化学
用于发现癌症治疗靶向蛋白降解剂的DEL-chemomics方法
DEL-chemomics approach for the discovery of targeted protein degraders for cancer therapy
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
DNA编码化学文库(DEL)技术已成为一种强大的苗头化合物鉴定工具，能够高效筛选大量编码化合物集合，在文库规模、成本和资源效率方面较传统高通量筛选具有优势。DEL的高化学多样性和编码保真度产生了大量数据，可支持诸如机器学习(ML)、3D药效团生成和基于结构的发现等计算方法。这一DEL-chemomics方法已应用于新型E3连接酶受体配体的发现，将E3配体的范围扩展到传统的CRBN和VHL之外，以降解药物靶点。本文将介绍DCAF1配体的发现及其在靶向WDR5降解的PROTAC中的应用案例研究。
查看英文原文 English abstract
DNA-encoded chemical library (DEL) technology has become a powerful tool for hit identification, enabling the efficient screening of large collections of encoded compounds with advantages over traditional high-throughput screening in terms of library size, cost, and resource efficiency. The high chemical diversity and encoding fidelity of DELs yields extensive data that can support computational approaches such as machine learning (ML), 3D pharmacophore generation and structure-based discovery. This DEL-chemomics approach has been applied to the discovery of novel E3 ligase receptor ligands, expanding the repertoire of E3 ligands beyond the traditional CRBN and VHL for degradation of drug targets. A case study of the discovery of DCAF1 ligand and its application in PROTACs that targeted WDR5 for degradation will be presented.
利益披露 Disclosure
Y. Zhang, None.