Molecular mechanisms of chronic diseases are complicated, and it impedes drug target identification and subsequent drug discovery. We consider entropy increase in human body the root causes of chronic diseases. Accordingly, the inherent neg-entropic mechanisms, for instance the homeostatic mechanisms for metabolism, immunity, self-healing, etc., are true drug targets. Only very few molecules (such as proteins) are decisive for neg-entropy related functions, thus they are termed "head goose molecules" (HGMs) here. Identification of HGMs is key to activating neg-entropic mechanism(s), and drug intervention of the HGMs' functions might reprogram the disease process through a neg-entropy mediated drug cloud (dCloud) effect, resulting in a treatment of both symptoms and root causes of the diseases. Thus, we recommend, for the first time, the "HGMs-neg-entropy-dCloud" axis as an important strategy for discovering new drugs. Clinically proven effective drugs that target HGMs are given as examples to illustrate the concept. Different from most of the single-target drugs that interrupt disease signal pathway(s), neg-entropy drugs treat chronic diseases through converting disorderliness to orderliness in the body of patients. We hope it to be helpful in future drug discovery for chronic diseases.
Keywords: Drug cloud; Entropy; Head goose molecules; Neg-entropy.
© 2025 The Authors.