School of Pharmacy , Second Military Medical University , 325 Guohe Road , Shanghai 200433 , China.
J Med Chem. 2018 Mar 22;61(6):2604-2610. doi: 10.1021/acs.jmedchem.8b00057. Epub 2018 Mar 13.
Targeting KRAS-PDEδ protein-protein interactions with small molecules represents a promising opportunity for developing novel antitumor agents. However, current KRAS-PDEδ inhibitors are limited by poor cellular antitumor potency and the druggability of the target remains to be validated by new inhibitors. To tackle these challenges, herein, novel, highly potent KRAS-PDEδ inhibitors were identified by fragment-based drug design, providing promising lead compounds or chemical probes for investigating the biological functions and druggability of KRAS-PDEδ interaction.
针对 KRAS-PDEδ 蛋白-蛋白相互作用的小分子药物代表了开发新型抗肿瘤药物的一个很有前途的机会。然而，目前的 KRAS-PDEδ 抑制剂受到细胞抗肿瘤效力差的限制，并且该靶点的成药性仍需要新的抑制剂来验证。为了解决这些挑战，本研究通过基于片段的药物设计，鉴定出了新型、高效的 KRAS-PDEδ 抑制剂，为研究 KRAS-PDEδ 相互作用的生物学功能和成药性提供了有前景的先导化合物或化学探针。
