First-in-class small molecule drugs in 2023 / 药学学报

In 2023, drug discovery develops steadily, with improvement of small molecule drugs discovery keeps pace with biological drugs in this year. The Center for Drug Evaluation and Research of U.S. Food and Drug Administration has totally approved 55 kinds of new drugs which have significantly promotion compared to 37 new drugs approval in 2022, including 38 kinds of new molecular entities, 17 kinds of biological drugs, 5 kinds of gene therapeutics and 2 cell therapeutics. The proportion of first-in-class drugs increased steadily, with 13 small molecule first-in-class drugs and 7 biological first-in-class drugs approved this year, mostly in the fields of cancer and rare diseases. Among them, a plurality of first-initiated small molecule drugs exhibits breakthrough significance, such as the first neurokinin 3 (NK3) receptor antagonist fezolinetant, the first retinoic acid receptor (RIG-I) agonist palovarotene, the first protein kinase B (AKT) inhibitor capivasertib, the first complement factor B inhibitor iptacopan, etc. The pioneering drug has huge academic and commercial value, and has become the target of the academic and industrial circles. However, first-in-class drugs not only need new targets, new mechanisms and new molecules, but also need to comprehensively verify the causality between new targets and diseases, study the correlation between new mechanisms and drug efficacy, and explore the balance between new molecules and drug-manufacturing properties. This article analyzed the research background, development process and therapeutic application of three first-initiated small molecule drugs in this year, expecting to provide more research ideas and methods for more first-in-class drugs.

Drugs that act in the lymphatic system and lymphatic drug delivery: review and perspective / 药学学报

The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.

EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations. @*Materials and Methods@#This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint. @*Results@#The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment. @*Conclusion@#EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.

Design of small molecules targeting molecular chaperone system: review and perspective / 药学学报

Molecular chaperone system, which mainly consist of heat shock proteins family and their cochaperones, is crucial for maintaining proteostasis in life. It assists in folding, maturation and ubiquitin-proteasome-mediated degradation of proteins, thus to play a key role in cell proliferation and apoptosis. Functional disorder of molecular chaperone system is highly relevant to occurrence and development of multiple diseases including cancers, autoimmune disease/inflammatory, infective diseases, neurodegenerative disease, etc. Therefore, molecular chaperone system has long been regarded as potential drug targets. In this review, we outline the progress in the design of small molecules targeting molecular chaperone system and analyze the features of small molecules with different mechanisms. Finally, we put forward expects about potential development directions for future drug design in this field.

First-in-class small molecule drugs in 2022 / 药学学报

2022 is the third year of the global COVID-19 pandemic, and its troubles on new drug discovery are gradually apparent. 37 new drugs were approved by the FDA's Center for Drug Evaluation and Research (CDER) last year, down from the peak of 50 new drug approvals in 2021. Notably, first-in-class drugs still occupy a dominant position this year, with a total of 21 drugs. Among them, 7 are first-in-class small molecule drugs. Although the total number of new drug approvals in 2022 sharply decreased, some first-in-class small molecule drugs were regarded as significant, including mitapivat, the first oral activator targeting the pyruvate kinase (PK); mavacamten, the first selective allosteric inhibitor targeting the myocardial β myosin ATPase; deucravacitinib, the first deuterated allosteric inhibitor targeting the tyrosine kinase 2 (TYK2); and lenacapavir, the first long-acting inhibitor targeting the HIV capsid. Generally, the research of first-in-class drugs needs to focus on difficult clinical problems and can treat some specific diseases through novel targets and biological mechanisms. There are tremendous challenges in the research processes of new drugs, including biological mechanism research, target selection, molecular screening, lead compound identification and druggability optimization. Therefore, the success of first-in-class drugs development has prominent guidance significance for new drug discovery. This review briefly describes the discovery background, research and development process and therapeutic application of 3 first-in-class small molecule drugs to provide research ideas and methods for more first-in-class drugs.

The development of small-molecule inhibitors targeting MYC / 药学学报

The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.

First-in-class small molecule drugs in 2020 / 药学学报

With the development of the research on innovative drugs in our country, first-in-class drugs are becoming a main goal for both pharmaceutical companies and scientific institutions. Discovery of first-in-class drugs require amounts of basic research, a massive investment and novel methods, acting as a beacon for the new drug development. In 2020, FDA totally approved 53 novel drugs with 38 small molecules, which still accounting for a major component. Among them, many first-in-class drugs are important including a first EZH2 inhibitor (tazemetostat) for the treatment of epithelioid sarcoma, a first attachment inhibitor (fostemsavir) with novel mechanism for the treatment of HIV, a first farnesyltransferase inhibitor (lonafarnib) for the treatment of Hutchinson-Gilford progeria syndrome (HGPS) and a first MC4 receptor agonist for the treatment of rare genetic diseases of obesity, etc. The research procedures of the above drugs are representative with new ideas. In this review, we outline 3 of the first-in-class drugs to discuss the research background, discovery and development process as well as the therapeutic potentials to provide methods and ideas for the further drug development.

Roles of highly expressed bone-specific genes in bone metastatic prostate cancer PC3 cells: Advances in studies / 中华男科学杂志

Prostate cancer (PCa) is a maligmancy with high morbidity and mortality. Bone metastasis is the main cause of short survival time and difficulties in the treatment and prevention of PCa. Previous findings of our team showed 155 bone-specific genes highly expressed in bone metastatic PC3 cells, which is considered to be the key to their adaptation to the bone micro-environment, proliferation and formation of metastatic tumor, and extensively exists in cancer metastasis in multiple systems. This review summarizes the published literature on the highly expressed bone-specific genes, focusing on the roles and values of these genes in the metastasis, progression, clinical diagnosis, treatment and prognosis of PCa, offering a prospect of the direction and targets in the studies of PCa bone metastasis so as to enrich the bone metastatic theories and clinical treatment principles of this disease in the future.

Design, synthesis and activity evaluation of protein arginine methyltransferase 5 inhibitor / 药学学报

Protein arginine methyltransferase 5 (PRMT5) is an important type II human methyltransferase. It catalyzes the symmetrical double-methylation of many histones and non-histones, and it is highly expressed in many kinds of tumors. PRMT5 has been proven to be a potential new target for cancer treatment. Based on the reported crystal complex of EPZ015666 with PRMT5, a series of new compounds was designed using GSK3326595 (EPZ015938) as the lead compound and using the conformational restriction approach. We found that compounds B8 and the C series of derivatives displayed enzyme inhibitory activity comparable to that of GSK3326595. Compounds C3 and C4 showed poor permeability in Caco-2 cells, and that might be one of the reasons for their poor anti-proliferative activity against Z-138 cells. These data provide insights for further structural optimization.

The development of small-molecule inhibitors that target PRC2-related proteins / 药学学报

Abnormal expression of polycomb repressive complex 2 (PRC2) is related to the development of a variety of diseases. Inhibition of normal or overactive PRC2 can reduce cell survival and inhibit tumor growth in several cancers. Therefore, the identification and development of small molecule inhibitors has become an active field of current epigenetic-related anti-tumor strategies. A small molecule inhibitor targeting the S-adenosyl-L-methionine (SAM) binding site of enhancer of zeste homologue 2 (EZH2) has been approved by FDA. However, acquired drug resistance is of concern. Drugs targeting two different binding sites of embryonic ectoderm development (EED) are also being developed. The development of EZH2-EED proton pump inhibitor has attracted extensive attention due to its unique mechanism of action. In this paper, we review the research progress on various small molecule inhibitors that target PRC2-related proteins to provide a basis for further research and development of related drugs.

First-in-class small molecule drugs in 2018 / 药学学报

In 2018, FDA approved 59 kinds of new drugs in all, breaking the record of 53 set in 1993. There were 34 types of small molecule drugs, which accounted for 64% of the whole new drugs. Of these 34 new small molecule drugs, 9 first-in-class ones marked a milestone for the subsequent drug discovery and development. These include Glasdegib, the world's first small molecule inhibitor targeting Smo through Hedgehog signaling pathway; Ivosidenib, the first small molecule inhibitor targeting mutant IDH1; Tecovirimat, the first small molecule drug for anti-variola virus therapy through targeting p37; Baloxavir marboxil, the first anti-flu drug targeting cap-dependent endonuclease; Elagolix sodium, the first small molecule inhibitor in treating endometriosis by targeting GnRH-R, etc. The research and development of first-in-class drugs is always full of obstacles and challenges. However, once they were successfully recognized as the "heavy bomb" drugs, they would become huge benefits. This article chose the representative first-in-class small molecule drugs that were approved in 2018 as examples to analyze their development processes in an attempt to provide guidance for the research and development of more first-in-class drugs.

Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF165 to the ischemic myocardium / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA3.1-human vascular endothelial growth factor 165 (pcDNA3.1-hVEGF165) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA3.1-hVEGF165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA3.1-hVEGF165 plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.

Causes of Failure during the Management Process from Identification of Brain-Dead Potential Organ Donors to Actual Donation in Korea: a 5-Year Data Analysis (2012–2016)

BACKGROUND: This retrospective study analyzed the causes of failure in the management process from the identification of brain-dead potential organ donors to actual donation in Korea over the past 5 years. METHODS: Data of 8,120 potential brain deaths reported to the Korea Organ Donation Agency were used, including information received at the time of reporting, donation suitability evaluation performed by the coordinator after the report, and data obtained from interviews of hospital medical staff and the donor's family. RESULTS: From January 2012 to December 2016, the total number of brain-dead potential organ donors in Korea was 8,120, of which 2,348 (28.9%) underwent organ procurement surgery with designated recipients. While the number of transplant donors has increased over time, the ratio of transplant donors to medically suitable brain-dead donors has decreased. The common causes of donation failure included donation refusal (27.6%), non-brain death (15.5%), and incompatible donation (11.6%); 104 potential donors (7.8%) were unable to donate their organs because they were not pronounced brain dead. CONCLUSION: The rate of successful organ donation may be increased by analyzing the major causes of failure in the brain-dead organ donation management process and engaging in various efforts to prevent such failures.

Effect of Qiangjing Tablets on the MAPK signaling pathway in SD rats with asthenospermia / 中华男科学杂志

<p><b>Objective</b>To investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).</p><p><b>METHODS</b>A total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.</p><p><b>RESULTS</b>The AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue (［9.20 ± 3.07］ vs ［42.20 ± 9.17］ %, P<0.01), but decreased level of TGF-β1 in the semen (［627.67 ± 26.07］ vs ［566.73 ± 68.44］ ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis (［42.20 ± 9.17］ vs ［21.60 ± 5.94］ %, P<0.01; ［42.20 ± 9.17］ vs ［33.95 ± 6.39］ %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group (［621.78 ± 30.80］ vs ［566.73 ± 68.44］ ng/ml, P < 0.05).</p><p><b>CONCLUSIONS</b>Qiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.</p>

Protein degradation as an innovative strategy in drug discovery / 药学学报

The success rate of mechanism-based drug discovery depends on the drug targets. With the rapid development of genomics and proteomics, a lot of nonenzymic proteins have been identified as potential drug targets. However, these nonenzymic proteins cannot be regulated by occupying the active site, which were recognized as undruggable targets. Direct regulation of the concentration of these proteins in cells by the innate ubiquitin-proteasome is a potential approach to target these proteins. The ubiquitination of target protein by E3 ligase is the key step for ubiquitin-proteasome mediated protein degradation. Proteolysis targeting chimeras (PROTACs) can facilitate the assembly of complex that consists of the target protein and E3 ligase. The target protein will be ubiquitinated, leading to the degradation by proteasome. This type of regulation mechanism can expand the scope of potential drug targets, and the development of PROTACs may be an innovative strategy in drug discovery.

HTRF-based method for determination of HSP90-HOP inhibition activity and its application / 药学学报

HSP90 is widely expressed in cells with the main function in assisting the maturation of other proteins that are called clients. Many clients play critical roles in the occurrence and development of cancer. Inhibition of HSP90 can lead to degradation of the oncogenic proteins, and result in potent anti-cancer effects. HSP90-HOP interaction is critical for the chaperone function of HSP90, thereby disruption of the HSP90-HOP interaction is a novel strategy in the inhibition of HSP90. Based on the technology of homogeneous time-resolved fluorescence (HTRF), we developed a new assay for the identification of new inhibitors of HSP90-HOP interaction. This method was evaluated in the study of the HSP90-HOP inhibition activity of the pentapeptide MEEVD from HSP90 C-terminal and its derivatives. This study can provide a basis for the screening and discovery of novel HSP90-HOP disruptors.

Expression of MCL-1 in Primary Acute Myeloid Leukemia Cells and Its Clinical Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect the expression of MCL-1 in patient with acute myeloid leukemia(AML) with normal karyotype and to investigate the relationship of its expression level with clinical parameters and prognosis.</p><p><b>METHODS</b>The expression of MCL-1 in the bone marrow from 37 newly diagnosed AML patients was measured by real-time fluorescent quantitative PCR(FQ RT-PCR) and Western blot, and the relationship between its expression level and clinical parameters such as the age, sex, WBC count, Hb level, Plt count, blast ratio in BM, and sensitivity to chemotherapeutic drugs in vitro prognosis was analyzed.</p><p><b>RESULTS</b>The expression level of MCL-1 did not correlate with the age, sex, WBC count, Hb level, Plt count and the percentage of blast cells. There was no significant difference of MCL-1 expression in AML patients with or without extramedullary infiltration. The higher level of MCL-1 existed in AML patients who did not achieve complete remission with classical regimen. The resistant rate to chemotherapeutic drugs in vitro was higher in the patients with higher level of MCL-1.</p><p><b>CONCLUSION</b>Overexpression of MCL-1 is closely related with the resistance to chemotherapeutic drugs, and may be used as an early indicator for judging multi-drug resistance and prognosis of AML.</p>

Alteration of microRNA expression in cerebrospinal fluid of unconscious patients after traumatic brain injury and a bioinformatic analysis of related single nucleotide polymorphisms / 中华创伤杂志(英文版)

<p><b>PURPOSE</b>It is becoming increasingly clear that genetic factors play a role in traumatic brain injury (TBI), whether in modifying clinical outcome after TBI or determining susceptibility to it. MicroRNAs are small RNA molecules involved in various pathophysiological processes by repressing target genes at the post- transcriptional level, and TBI alters microRNA expression levels in the hippocampus and cortex. This study was designed to detect differentially expressed microRNAs in the cerebrospinal fluid (CSF) of TBI patients remaining unconscious two weeks after initial injury and to explore related single nucleotide polymorphisms (SNPs).</p><p><b>METHODS</b>We used a microarray platform to detect differential microRNA expression levels in CSF samples from patients with post-traumatic coma compared with samples from controls. A bioinformatic scan was performed covering microRNA gene promoter regions to identify potential functional SNPs.</p><p><b>RESULTS</b>Totally 26 coma patients and 21 controls were included in this study, with similar distribution of age and gender between the two groups. Microarray showed that fourteen microRNAs were differentially expressed, ten at higher and four at lower expression levels in CSF of traumatic coma patients compared with controls (p<0.05). One SNP (rs11851174 allele: C/T) was identified in the motif area of the microRNA hsa-miR-431-3P gene promoter region.</p><p><b>CONCLUSION</b>The altered microRNA expression levels in CSF after brain injury together with SNP identified within the microRNA gene promoter area provide a new perspective on the mechanism of impaired consciousness after TBI. Further studies are needed to explore the association between the specific microRNAs and their related SNPs with post-traumatic unconsciousness.</p>

Combination of Homoharringtonine with Arsenic Trioxide Induces Apoptosis of Human Acute Myeloid Leukemia Cell Line U937 / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects and mechanisms of the combination of homoharringtonine (HHT) with arsenic trioxide(AsO) on human myeloid cell line U937 in vitro.</p><p><b>METHODS</b>MTT method was used to determine the antiproliferating effect of different concentrations of HHT, AsOand their combination on U937 cells; the flow cytometry with Annexin-V-FITC/PI double staining was used to determine the apoptosis-induced effect of HHT and AsOalone or their combination; Western blot method was used to detect the protein expression of P-Akt,P-Akt,BCL-XL, BID,MCL-1,P-MCL-1 and so on.</p><p><b>RESULTS</b>HHT and AsOcould significantly inhibit proliferation of U937 cells and induce their apoptosis. The combination of these 2 drugs could significantly enhance the early apoptosis of U937 cells. After combination of these 2 drugs was used, the protein expressions of P-Akt,P-Akt,MCL-1,P-MCL-1 and BCL-XL were obviously down-regulated, but the expression of BID protein did not change.</p><p><b>CONCLUSION</b>The combination treatment of HHT and AsOcan synergistically inhibit the growth of U937 cells through inhibition of PI3K/Akt signal way and MCL-1 protein.</p>

Inhibitory effect of Qiangjing Tablets on the Fas/FasL pathway of cell apoptosis in male SD rats with infertility / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.</p><p><b>METHODS</b>Models of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.</p><p><b>RESULTS</b>Compared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>By upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.</p>