Details

Autor(en) / Beteiligte

• Peng, Jian
• Zeng, Yisheng
• Hu, Xiaojun
• Huang, Sheng
• Gao, Xiaofang
• Tian, Dong
• Tian, Shuting
• Qiu, Lan
• Liu, Jin
• Dong, Renhan
• Zhan, Wei
• Qin, Chuanjun
• Guang, Bing
• Yang, Tai

Titel

KC-180‑2 Exerts Anti-SCLC Effects via Dual Inhibition of Tubulin Polymerization and Src Signaling

Ist Teil von

• ACS omega, 2022-09, Vol.7 (36), p.32164-32175

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• In this study, a series of N-benzyl-2-(5-phenylpyridin-2-yl) acetamide-based derivatives were successfully designed and synthesized as anti-cancer agents. KC-180-2 was screened as a potentially leading compound with dual mechanisms of action: Src signaling and tubulin polymerization inhibition. It efficiently suppressed the proliferation of five cancer cell lines (MDA-MB-231, H446, SKOV-3, HepG2, and HT29), with IC50 values ranging from 5 to 188 nM, especially small-cell lung cancer (SCLC) cells (IC50, 5 nM). Correspondingly, it exerted a significant therapeutic effect on the H446 small-cell lung cancer xenograft model, significantly reducing the volume of tumors without obvious toxicity. Mechanistically, this compound significantly inhibited the polymerization of purified tubulin in vitro, inducing G2/M cell cycle arrest and binding to the kinase catalytic domain of the Src protein, which reduced the phosphorylation of Src. Thus, KC-180-2 is a potential lead compound for the further development of a new anti-tumor drug against SCLC.