WDR5-degrader-E3 ligase ternary complex structure–based design led to a highly effective WDR5 degrader with robust in vivo antitumor activities.

Myricetin (3,5,7,3′,4′,5′-hexahydroxyflavone) is one of the natural flavonols from fruit, vegetable, tea, and medicinal plants. A great deal of attention has been paid to this compound owing to its various health-promoting effects. In this review, we provide a comprehensive discussion of the therapeutic potential of myricetin by focusing on its biological activity and pharmacokinetic properties.

Proteolysis targeting chimeras (PROTACs), heterobifunctional molecules that hijack the ubiquitin–proteasome system (UPS) to degrade specific proteins, hold great promise in treating diseases driven by traditionally “undruggable” targets. However, their large molecular weight, high hydrophobicity, and other physicochemical hurdles contribute to their limited bioavailability, suboptimal pharmacokinetics, and attenuated therapeutic efficacy. Consequently, diverse formulation innovations have been investigated to optimize PROTAC delivery. This review examines current challenges and advances in specialized drug delivery approaches designed to bolster PROTAC pharmacological performance. We first outline the fundamental limitations of PROTACs—their low aqueous solubility, poor cell permeability, rapid clearance, and concentration-dependent “hook effect”. We then discuss how various enabling formulations address these issues, including polymeric micelles, emulsions, amorphous solid dispersions, lipid-based nanoparticles, liposomes, and exosomes. Collectively, these delivery technologies substantially improve the therapeutic outcomes of PROTACs in preclinical cancer models. Future applications may extend beyond oncology to address other complex diseases using newly emerging heterobifunctional molecules. By integrating advanced formulation science with innovative degrader design, the field stands poised to unlock the clinical potential of PROTACs for protein degradation therapies.