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  • Yan-quan YANG, Jian-guo SUN, Ji-ye A, Guang-ji WANG, Ying PENG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2155-2167.

    The medicinal history of Pien Tze Huang is long, and it is the only "double top secret" variety of technology and formula at present. It has the effects of clearing heat and detoxifying, detumescence and pain, cooling blood and removing blood stasis. At present, researchers have analyzed and identified some compounds in Pien Tze Huang and its precious medicinal materials, such as Panax notoginseng, calculus bovis, snake gall and musk, and conducted activity screening, pharmacokinetics and pharmacological related studies on these chemical components. It was found that Pien Tze Huang had a significant effect on the treatment of acute and chronic hepatitis, ulcer, colon cancer, liver cancer and other diseases. The purpose of this paper is to systematically discuss the research achievements of researchers in recent years on the material basis, pharmacological effects and clinical application of Pien Tze Huang, with a view to providing ideas for the further research of Pien Tze Huang.

  • Shi-fen LI, Ruo-xuan YANG, Jian SUN, Hai-hai LIANG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2168-2179.

    Astragalus, which was first documented in Shennong Bencao Jing, is the dried root of Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao. The active ingredients astragalus membranaceus saponins (AMS), astragalus polysaccharides (APS) and astragalus flavonoids (AFS) have pharmacological effects such as anti-tumor properties, lowering blood sugar, regulating lipid metabolism, cardiovascular protection, anti-oxidation, bone protection, anti-fibrosis, etc. Fibrosis affects almost all organs, particularly vital organs such as the lungs, liver, heart and kidneys. The primary pathological changes of fibrosis involve abnormal increase of myofibroblasts and excessive deposition of extracellular matrix (ECM) components, which lead to the formation of scar tissue, ultimately resulting in fibrosis and even functional loss or failure of organs, which seriously threatens human health and life. Recent, studies have shown that Astragalus membranaceus has a good therapetuic effect on organ fibrosis. This article reviews the current advances of Astragalus in the prevention and treatment of fibrosis of lungs, liver, heart, kidneys and other important organs.

  • Ke-liang LI, Yang LIU, Chun-yang LOU, Tian-le HUANG, Zhan-ying HONG, Shan-chao WU, Chun-quan SHENG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2180-2192.

    Cancer seriously threatens human life and health, it is urgent for the development of rapid detection, precise localization and effective treatment of tumors. Chemical fluorescent probes that are sensitive to tumor-specific microenvironments have important significance in tumor theranostics and a variety of such probes have been developed. In this review, we classified chemical fluorescent probes that are sensitive to tumor microenvironments according to biological characteristics and microenvironmental changes while combining spectroscopy or response mechanisms, and systematically introduced the research progress of chemical fluorescent probes with sensitivity to hypoxia, low polarity, high viscosity, abnormal pH values and abundant reactive oxygen species in tumor microenvironments, in order to provide references for the development and applications of these probes.

  • Yi MOU, Shuai WEN, Yan WANG, Zheng-yu JIANG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2193-2202.

    Proteolysis targeting chimeras (PROTACs) is an innovative technique in targeted protein degradation. PROTACs is a heterobifunctional molecule which can bind to the E3 ligase and target protein to form a ubiquitination complex, resulting in the ubiquitin-proteasome system dependent degradation of target protein. PROTACs has been regarded as the promising method in drug discovery campaign, for its high commonality, potent degradation activity and unique selectivity profile. However, the catalytic mechanism also induces the uncontrollable protein degradation risk. Controllable PROTACs contain the responsive element in the molecular entity. In certain conditions, the element can be triggered to activate or terminate the degradation event. In this review, we will briefly summarize the strategies in controllable PROTACs and describe the representative examples according to the responsive mechanism. We hope this review could provide some insight into the further development of controllable PROTACs.

  • Yang ZHOU, Shu-jing XU, Dang DING, Shuo WANG, Xin-yong LIU, Peng ZHAN
    Acta Pharmaceutica Sinica. 2023, 58(8): 2203-2217.

    To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

  • Tian CAI, Bing-hao KANG, Yue CHENG, Min HUANG, Lin-xiang ZHAO
    Acta Pharmaceutica Sinica. 2023, 58(8): 2218-2225.

    The most toxic DNA damage is DNA double strand breaks (DSBs), which are mainly repaired by non-homologous end joining (NHEJ). DNA-dependent protein kinase (DNA-PK) belongs to phosphatidylinositol-3-kinase-related protein kinase family (PIKK) and plays a key role in NHEJ. DNA-PK is overexpressed in a variety of cancer cells and is related to the occurrence, development and drug resistance of malignant tumors. In this article, the representative DNA-PK inhibitors with anticancer effects are reviewed, in order to provide a reference to discovery novel DNA-PK inhibitors.

  • Xin-yu YANG, Jia-wen SHANG, Hai-yun YU, Yi-hui SONG, Bin YU
    Acta Pharmaceutica Sinica. 2023, 58(8): 2226-2238.

    Src homology phosphotyrosyl phosphatase 2 (SHP2) is a protein tyrosine phosphatase encoded by PTPN11, which catalyzes the dephosphorylation of protein tyrosine. As a convergence node, SHP2 mediates multiple signaling pathways such as rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated extracellular signal-regulated kinase (MEK)-extracellular regulated protein kinases (ERK), phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT), janus kinase (JAK)-signal transducer and activator of transcription (STAT) and programmed death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1). It can not only regulate the growth and proliferation of tumor cells, but also mediate the immune escape of tumor cells by influencing the tumor microenvironment. Given its dual biological functions in tumor immune regulation, SHP2 is a promising target for cancer immunotherapy. To date, several SHP2 allosteric inhibitors have been advanced into clinical trials for tumor immunotherapy with single or combination therapeutic strategies. Additionally, SHP2 activators also showed therapeutic potential in the field of tumor immune modulation. In this paper, we reviewed the dual function of SHP2 in both tumor and immune cells. Besides, the challenges and prospects of SHP2 modulators in cancer immunotherapy were also briefly discussed, aiming to explore new horizon of SHP2 modulators for tumor immunotherapy.

  • Jia-hua KE, Dan-lei CHEN, Kui CHENG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2239-2249.

    Toll like receptors (TLRs) are the earliest discovered natural immune pattern recognition receptors (PRRs). The abnormality of TLR signal transduction pathway is the key factor leading to chronic inflammatory, cancer, nervous system disease and cardiovascular diseases. The development of TLR agonists and inhibitors has attracted much attention. Currently known TLR2 agonists, such as lipopeptides or their derivatives, have certain limitations in drug development due to their difficult synthesis, easy hydrolysis, and triggering inflammatory cytokine storms, while inhibitors have been rarely reported. New small molecule TLR2 agonists or inhibitors with higher stability are more likely to be developed as tumor immunotherapy or anti-inflammatory drugs.

  • Chen CHEN, Yi-xin CHEN, Chong-jing ZHANG
    Acta Pharmaceutica Sinica. 2023, 58(8): 2250-2259.

    Small molecule fluorescent probes have gained widespread attention for their advantages of high selectivity, sensitivity, and easy to operate, and have played a critical role in the detection of various species. They have also demonstrated great potential in the field of biomedical research. Iron, as the most abundant transition metal in the human body, plays a vital role in many physiological functions. Due to the influence of the reductive microenvironment of cell, ferrous ion (Fe2+) is the main component of labile iron in living cells. Heme, consisting of Fe2+ and protoporphyrin IX, is one of the main signaling molecules that wrap biological iron in the human body, and also participates in many physiological and pathological processes. Therefore, the development of small molecule fluorescent probes for detecting Fe2+ and heme as effective monitoring tools will help to further understand their pathological and physiological functions, with potential applications in other fields. This review summarizes the research progress of small molecule fluorescent probes for Fe2+ and heme detection in recent years, and provides insights into future directions for their development.

  • Li-xing NIE, Yan-pei WU, Jing LIU, Xiao-ru HU, Feng-yan HE, Ya-dan WANG, Qi WANG, Jian-dong YU, Zhong DAI, Feng WEI, Shuang-cheng MA
    Acta Pharmaceutica Sinica. 2023, 58(8): 2260-2270.

    Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.