Highlights

• This patent describes a novel small-molecule inhibitor, ZYZ-384, of histone methyltransferase SMYD3, which inhibits SMYD3 enzymatic activity in a dose-dependent manner and significantly suppresses the proliferation of various cancer cells.
• In vivo experiments showed that the compound effectively inhibited orthotopic liver tumor growth, reduced intratumoral SMYD3 protein expression, and exhibited good safety and drug-like properties, offering a new strategy for developing anti-cancer drugs targeting SMYD3.

Summary

This invention patent focuses on the development of a small-molecule inhibitor of histone methyltransferase SMYD3, named ZYZ-384, and its anti-tumor mechanism of action. Through computer-aided virtual screening and rational design, a novel SMYD3 inhibitor with a new structure was synthesized. It was confirmed to inhibit SMYD3 enzymatic activity in a dose-dependent manner and effectively suppress the proliferation of various cancer cells, including liver cancer, lung cancer, and colon cancer.

Notably, this inhibitor demonstrated good safety and significant liver cancer suppression effects in mouse models, and it reduced SMYD3 protein expression levels in tumor tissues.

Through multiple experimental approaches (including biolayer interferometry, molecular docking, and in vitro and in vivo pharmacological evaluations), the patent clarified the binding mechanism between ZYZ-384 and SMYD3, and highlighted its potential as an anti-cancer drug candidate. The results suggest that targeting SMYD3 with small-molecule inhibitors holds significant promise in cancer therapy.

王晓琳, 朱依谆, 唐桩, 孟诗雨, “Preparation Method and Application of a Biomimetic Liposomal Drug Delivery System Targeting Ischemic Stroke,” China Patent CN114557978B, Mar. 3, 2023.