中药(Traditional Chinese Medicines，TCMs)作为天然产物的重要组成部分，在现代药物研发中引起了广泛关注。与单靶标作用相比，中药通过多组分、多靶标、多途径的全面协同作用，在治疗复杂疾病时具有提高疗效、降低副作用等优势。近年来，中药已被认为是一种有价值的潜在的新型抗癌药物。 丝氨酸在很多细胞过程中扮演重要角色，它参与构成核酸、脂质、氨基酸和辅基，与细胞增殖相关。依据正常细胞和癌细胞之间的代谢差异，我们将目光放在了参与癌细胞代谢的关键酶身上。人体中的D-3-磷酸甘油酸脱氢酶(PHGDH)是催化丝氨酸合成的决速步骤，PHGDH异常表达现象在许多癌症中也陆续被发现。研究证实，PHGDH基因的敲除会大幅度抑制这些癌细胞在体内以及体外的生长。因此，PHGDH被视为一个有很大发展潜力的抗癌靶标。 2016年，PHGDH的抑制剂相继被发现，但仍存在很大的发展空间。目前所发现的抑制剂大多为非竞争性抑制剂，作用机理也还待验证。至今还没有靶向 PHGDH的草药或者天然产物报道。本文采用理论和实践相结合的方法，筛选出体外活性较好的PHGDH中药小分子抑制剂。首先以PHGDH的结构为基础，从中药中筛选了可以与PHGDH结合的草药和化合物。接着通过一系列酶活实验、细胞实验，进一步检测化合物的活性，最终，筛选出具有活性中药化合物苦参醇F和苦参酮。苦参醇F和苦参酮的半抑制浓度IC50值分别为35 μM和104 μM，癌细胞的半致死率EC50分别为4.8μM和13μM。此外，经过对化合物结合机制的探究，初步认为苦参酮与PHGDH发生了共价结合。 这个工作首次发现了来源于天然产物的PHGDH的抑制剂，它为PHGDH抑制剂的发现提供了新思路，同时，也为发现其它蛋白的中药调控分子提供了高效且可行的策略。

Traditional Chinese Medicines (TCMs), as an important part of natural products, have attracted much attention in the discovery of modern drugs. Compared with the single target, TCMs has the advantages of improving the curative effect and reducing the side effect through the multi-component, multi-target and multi-channel comprehensive synergistic effect. In recent years, TCMs has been considered as a potential anti-cancer drugs. Serine plays an important role in many cell processes, and it participates in the formation of nucleic acids, lipids, amino acids and cofactors, associated with cell proliferation. Based on the metabolic differences between normal cells and cancer cells, we will focous on the key enzymes involved in the metabolism of cancer cells. D-3-phosphoglycerate dehydrogenase (PHGDH) is the first step of catalyzing serine synthesis. PHGDH abnormal expression is found in many cancer cells. Studies have confirmed that PHGDH gene knockout will greatly inhibit these cancer cells growth in vivo and in vitro. Therefore, PHGDH is viewed as a promising anti-cancer target. PHGDH inhibitors were first discovered in 2016, it still have great prospects for development. Most of the inhibitors found are noncompetitive inhibitors, the mechanism of action is also to be verified. There have been no reports about PHGDH inhibitors which from herbs or natural products. In this paper,we found PHGDH inhibitors from Sophora flavescens in vitro. First of all, based on the structure of PHGDH, we did the selection from TCMs which can be combined with PHGDH. Then we through a series of enzyme activity experiments and cell experiments to further detect the activity of the compound, and ultimately, we screened out Kushenol F and Kurainone. The IC50 values of Kushenol F and Kurainone are 35 μM and 104 μM, respectively, and EC50 of cancer cells was 6 μM and 12 μM.Though the exploration of combination mechanism,we think Kurainone is covleant bond to PHGDH. This work for the first time found inhibitors of PHGDH derived from natural products, which provides a new idea for the discovery of PHGDH inhibitors.At the same time, it provides an efficient and viable strategy for the discovery of other proteins from TCMs.