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.
Shan et al. (Fri,) studied this question.