Label-Free Target Discovery Strategy for Natural Active Products

The growing interest in harnessing natural compounds for health and medical applications underscores the necessity for innovative approaches to decipher their mechanisms of action. Among diverse strategies, non-probe-based methods for identifying the molecular targets of compounds represent one of the frontiers in drug discovery. This review focuses on an array of non-probe techniques for unveiling interactions between natural molecules and biological targets. The advantages and limitations of label-free protein target identification schemes suitable for lysed cells and living cells are analyzed. High-throughput target screening methods and their role in facilitating a holistic understanding of compound–target interactions are summarized. Based on comprehensive evaluation and comparison, this review aims to provide guidelines for selecting appropriate non-probe strategies to accelerate the characterization of the therapeutic potential of natural compounds.