Jinfei Yang

Hexokinase 2 (HK2) is an important target in cancer metabolism because it supports both glycolytic flux and mitochondria-associated survival signaling. In recent years, multiple HK2-directed strategies have emerged, including active-site inhibitors, repurposed scaffolds, electrophilic glycolysis blockers, and targeted protein degraders. Although several compounds have shown promising antitumor activity in preclinical models, their translation has been constrained by high structural similarity to HK1, the polarity and exposure liabilities of glucose-mimetic chemotypes, and, in some cases, limited mechanistic specificity. This review summarizes recent progress in HK2 inhibitor and degrader discovery, highlighting representative chemotypes, structure–activity relationships, pharmacological properties, and translational considerations. We also discuss opportunities for future development, including isoform-selective design, disruption of HK2–mitochondrial interactions, improved delivery strategies, and rational combination approaches. Overall, HK2 remains a promising but pharmacologically challenging target for cancer therapy.

A visible light‐driven E‐selective semihydrogenation scheme of alkyne compounds is developed for designing and synthesizing glioblastoma multiforme inhibitors. Herein, room‐temperature semihydrogenation reactions of various alkyne compounds are successfully achieved under the irradiation of white light. The representative reaction mechanism is decoded through theoretical calculations and deuteration experiments, revealing the critical roles played by [Ir(Cp‐Me₅)Cl₂]₂, PdCl₂, DPPE and TEOA as photosensitizer, catalyst, ligand, and electron donor, respectively. This method exhibits excellent E‐selectivity and broad functional group compatibility and demonstrates its practical value by producing pinosylvin and its derivatives with strong inhibitory effects on U87 cells.

As research on AD has progressed, TCM and its active ingredients have increasingly played a crucial role in clinical treatment. This article summarizes extracts from TCM and briefly elucidates their pharmacological mechanisms against AD.