A patent review of MLKL modulators (2023 - present).

Abstract

Introduction: Mixed-spectrum kinase structural domain-like protein (MLKL), which emerged as a pivotal regulator in biomedical research, plays a critical role in necroptotic pathways. Recent advancements have underscored the therapeutic potential of MLKL modulators.

Areas covered: This review focuses on the patent literature covering MLKL-targeted molecules published from 2023 to July 2025. Patent and literature searching were performed using SciFinder, Espacenet, and PubMed databases.

Expert opinion: Research on MLKL modulators has seen significant progress in recent years, with many preclinical studies documenting various modulators, but the development of MLKL modulators, particularly activators, remains in its early stages due to challenges in specificity, efficacy, and bioavailability. Advancing therapeutic strategies will require a deeper understanding of MLKL-driven pathologies, optimizing existing modulators, and discovering new ones. The notable increase in natural product-derived MLKL inhibitors highlights the potential of identifying and modifying natural products as an effective approach for developing novel inhibitors.