Synthesis and application of clinically approved small-molecule drugs targeting androgen receptor.

Androgen receptor (AR) plays a crucial role in various physiological processes. Dysregulation of AR signaling has been implicated in several diseases, such as prostate cancer and androgenetic alopecia. Therefore, the development of drugs that specifically target AR has gained significant attention in the field of drug discovery. This review provides an overview of the synthetic routes of clinically approved small molecule drugs targeting AR and discusses the clinical applications of these drugs in the treatment of AR-related diseases. The review also highlights the challenges and future perspectives in this field, including the need for improved drug design and the exploration of novel therapeutic targets. Through an integrated analysis of the therapeutic applications, synthetic methodologies, and mechanisms of action associated with these approved drugs, this review facilitates a holistic understanding of the versatile roles and therapeutic potential of AR-targeted interventions. Overall, this comprehensive review serves as a valuable resource for medicinal chemists interested in the development of small-molecule drugs targeting AR.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

[Effect of Sijunzi Decoction on regulation of Aß-related proteins across blood-brain barrier].

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aß_(25-35) oligomers(final concentration 40 µmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aß_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aß-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 µmol·L~(-1) Aß_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aß_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aß_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aß_(25-35) transport across the blood-brain barrier.

Effect of Zhenxin Xingshui Yizhi Fang on Aß25-35 induced expression of related transporters in HBMEC cell model.

ETHNOPHARMACOLOGICAL RELEVANCE: Aß (ß-amyloid) deposition and abnormal transport were suggested to be risk factors for Alzheimer's disease (AD). Zhenxin Xingshui Yizhi Fang (XSF), an ancient prescription in traditional Chinese medicine, was first recorded in Qianjin Yifang for treating palpitation, hypnosia, amnesia. It is reported that XSF could improve mice learning memory ability, reduce the deposition of senile plaques in hippocampus of rat brain. In this study, the neuroprotective effect of XSF against Aß25-35-induced apoptosis in cultured human brain microvascular endothelial cells (HBMEC) and its potential mechanism were investigated. MATERIALS AND METHODS: HBMEC cells were treated with Aß25-35 to established neurotoxic cell model. After that, the cells were treated with 125, 250, 500 µg/mL XSF to observe the protective effect. The viability of HBMEC cells were evaluated by MTT assay, the Aß25-35-induced apoptosis was characterized by Hoechst-33258 and the activity of cysteinyl aspartate specific proteinase-3. The expression level of Aß1-42 in cells induced by Aß25-35 was measured by human Aß1-42 kit. Protein and mRNA expression levels of advanced glycation end products (RAGE), low density lipoprotein receptor-related protein 1 (LRP1), glucose transporter 1 and 3 (GLUT1 and GLUT3) were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. RESULTS: In Aß25-35 induced neurotoxic cells, the percentage of apoptotic cells, the concentration of Aß1-42 and CASPASE-3 activity, protein and mRNA expression levels of RAGE increased significantly, but that of LRP1, GLUT1 and GLUT3 significantly decreased. XSF could inhibit the apoptotic of cells, reduced the concentration of Aß1-42 and CASPASE-3 expression, downregulate RAGE and upregulate LRP1, GLUT1 and GLUT3 expression. CONCLUSION: The results suggest that XSF can reduce the cytotoxicity of HBMEC induced by Aß25-35, inhibit apoptosis, and regulate the transport of Aß on BBB and energy metabolism disorder in HBMEC.