Design, synthesis, and evaluation of dual son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR) inhibitors for the treatment of cancers.

Bioorg Chem

Department of Medicinal Chemistry, School of Pharmacy, and Institute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing 211198, China. Electronic address:

Published: December 2024

The treatment of KRAS mutant tumors remains challenging and dual-targeted small-molecule drugs are considered to be innovative therapeutic alternatives. Herein, we discovered a series of SOS1 and EGFR dual inhibitors by employing a fused pharmacophore strategy and structural optimization. Notably, compound 4 exhibited potent SOS1 (IC = 8.3 nM) and EGFR (IC = 14.6 nM) inhibitory activities and markedly inhibited the proliferation of other KRAS-mutant cancer cell lines. Furthermore, Western blot analysis confirmed that compound 4 effectively reduced the level of downstream p-ERK. These results indicated that compound 4 could serve as a potential compound for treating KRAS mutant tumors.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2024.107833DOI Listing

Publication Analysis

Top Keywords

kras mutant
8
mutant tumors
8
design synthesis
4
synthesis evaluation
4
evaluation dual
4
dual son
4
son sevenless
4
sevenless sos1
4
sos1 epidermal
4
epidermal growth
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!