1.Clinical Evaluation of New Chinese Herbal Medicines for Syndromes: A Preliminary Study on Target Design
Li ZHANG ; Mengyuan ZHONG ; Yongfa XING ; Duojing LI ; Zheying WU ; Yuhong HUANG
Journal of Traditional Chinese Medicine 2024;65(16):1730-1733
There are certain limitations in the current clinical evaluation methods and evaluation modes of new Chinese herbal medicines for syndromes, and there is a lack of a clinical evaluation system that meets the characteristics of traditional Chinese medicine (TCM). Based on the characteristics of TCM "syndrome differentiation and treatment" and "correspondence of formulas and syndromes", the target design model, hypothesis and its scope of application are proposed on the basis of the combination of diseases and syndromes. On the basis of fully considering the dual factors of diseases and syndromes, we distinguished the "centre of the target", "middle ring" and "outer ring" through the differences of different signs and symptoms in people with same syndrome, in order to determine the degree of conformity of the syndrome. Then, the population with same syndrome could be analysed according to the "centre of the target", "middle ring" and "outer ring", so as to achieve the precise positioning of new Chinese herbal medicines for syndromes, and try to provide research ideas and methods for syndrome differentiation and treatment of TCM and precise intervention.
2.Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment.
Hongyu WU ; Hong YAO ; Chen HE ; Yilin JIA ; Zheying ZHU ; Shengtao XU ; Dahong LI ; Jinyi XU
Acta Pharmaceutica Sinica B 2022;12(9):3548-3566
Molecular glues can specifically induce aggregation between two or more proteins to modulate biological functions. In recent years, molecular glues have been widely used as protein degraders. In addition, however, molecular glues play a variety of vital roles, such as complex stabilization, interactome modulation and transporter inhibition, enabling challenging therapeutic targets to be druggable and offering an exciting novel approach for drug discovery. Since most molecular glues are identified serendipitously, exploration of their systematic discovery and rational design are important. In this review, representative examples of molecular glues with various physiological functions are divided into those mediating homo-dimerization, homo-polymerization and hetero-dimerization according to their aggregation modes, and we attempt to elucidate their mechanisms of action. In particular, we aim to highlight some biochemical techniques typically exploited within these representative studies and classify them in terms of three stages of molecular glue development: starting point, optimization and identification.