Chemical Biology & Drug Design最新文献

{"title":"Synthesis and Preliminary Anticancer Evaluation of 4-C Derivatives of Diphyllin","authors":"Ruihan Zhao,&nbsp;Xiao Ni,&nbsp;Chenhu Dong,&nbsp;Jun Xu,&nbsp;Yu Zhao","doi":"10.1111/cbdd.14635","DOIUrl":"10.1111/cbdd.14635","url":null,"abstract":"<div>\u0000 \u0000 <p>The natural lignan diphyllin has shown promising antitumor activity, although its clinical advancement has been impeded by challenges such as low solubility, poor metabolic stability, and limited potency. In response, we developed and synthesized two sets of diphyllin 4-<i>C</i> derivatives, comprising six ester derivatives and eight 1, 2, 3-triazole derivatives. Notably, among these derivatives, 1, 2, 3-triazole derivatives <b>7c</b> and <b>7e</b> demonstrated the most potent cytotoxic effects, with IC₅₀ values ranging from 0.003 to 0.01 μM. Treatment with 0.2 μM of <b>7c</b> and <b>7e</b> resulted in a reduction of V-ATPase activity in HGC-27 cells to 23% and 29%, respectively.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arctigenin Modulates Adipogenic-Osteogenic Balance in the Bone Marrow Microenvironment of Ovariectomized Rats via the MEK1/PPARγ/Wnt/β-Catenin Pathway","authors":"Hongbo Li,&nbsp;Xingen Liao,&nbsp;Min Lan,&nbsp;Jianying He,&nbsp;Jingping Gao,&nbsp;Zhiqiang Fan,&nbsp;Jiayu Huang,&nbsp;Xin Wu,&nbsp;Jiaxin Chen,&nbsp;Guicai Sun","doi":"10.1111/cbdd.14625","DOIUrl":"https://doi.org/10.1111/cbdd.14625","url":null,"abstract":"<div>\u0000 \u0000 <p>Arctigenin (Ar) is a promising therapeutic candidate for postmenopausal osteoporosis (PMOP). This study explores its mechanism by examining its effects on adipogenesis and osteogenesis in ovariectomized (OVX) rats. In vitro, Ar effectively suppressed the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) from OVX rats, reducing lipid droplet formation and downregulating proteins associated with lipid synthesis. In vivo, Ar treatment significantly reduced bone loss, inhibited adipocyte development, improved lipid metabolism, and promoted bone formation in OVX rats. Mechanistically, Ar inhibited the phosphorylation of Mitogen-Activated Protein Kinase 1 (MEK1), downregulated Peroxisome Proliferator-Activated Receptor gamma (PPARγ), promoted the accumulation of β-catenin in the nucleus, and prevented the direct binding of PPARγ to β-catenin in BMSCs. This regulation of the PPARγ/Wnt signaling axis underlies its dual role in inhibiting adipogenesis and promoting osteogenesis. Notably, co-treatment with rosiglitazone (RGZ) reversed the effects of Ar on adipogenesis and osteogenesis without affecting MEK1 inhibition. These findings offer valuable insights into arctigenin's potential as a therapeutic strategy for PMOP by modulating MEK1 signaling and regulating the PPARγ/Wnt axis.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalein Targets MAPK9 to Induce Apoptosis of Hepatocellular Carcinoma Cells","authors":"Weili Wang,&nbsp;Yuxiao Tang,&nbsp;Xiaobin Zhuo,&nbsp;Jianxin Yang,&nbsp;Zelong Gao,&nbsp;Chenqi Li,&nbsp;Chenghua Wu,&nbsp;Jianxin Qian,&nbsp;Feng Xie,&nbsp;Hui Shen,&nbsp;Dongyao Wang","doi":"10.1111/cbdd.14623","DOIUrl":"https://doi.org/10.1111/cbdd.14623","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is a significant global health concern. However, there are limited effective treatments available for it. The use of natural products in the management and treatment of HCC is gaining more attention. Baicalein is a flavonoid compound that has been reported to have antitumor activities in HCC. However, the direct binding targets of baicalein are still unknown. Therefore, we used the DNA-programmed affinity labeling method to identify the target of baicalein and validated its function in HCC cells. We set blank and competitive DNA probes as negative controls. The results showed that baicalein had 136 binding targets, of which 13 targets were differently expressed in HCC tissues. The enriched cellular process of these targets was apoptosis, which involved MAPK9. We tested the binding affinity of baicalein with MAPK9 as 89.7 nM (Kd) by surface plasmon resonance and analyzed the binding sites by virtual docking. Notably, the binding of baicalein with MAPK9 increased the protein levels of MAPK9 itself and the related downstream apoptosis signaling, triggering the apoptosis of HCC cells. However, the inhibitor of MAPK9, SP600125, blocked the baicalein-induced apoptosis, and the amounts of MAPK9 and downstream molecules were also decreased, indicating that baicalein acted through MAPK9 to induce apoptosis of HCC cells. In conclusion, we used the DNA-programmed affinity labeling method to identify the direct-binding target MAPK9 of baicalein and validated its function in baicalein-induced apoptosis of HCC cells, which would be helpful to understand and use baicalein in HCC therapy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoquercetin Ameliorates Osteoarthritis via Nrf2/NF-κB Axis: An In Vitro and In Vivo Study","authors":"He Yu,&nbsp;Junsheng Lou,&nbsp;Libin Ni,&nbsp;Minwei Yan,&nbsp;Kewu Zhu,&nbsp;Su Mao,&nbsp;Jungao Zhu","doi":"10.1111/cbdd.14620","DOIUrl":"https://doi.org/10.1111/cbdd.14620","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoarthritis (OA) is a progressive joint disease characterized by extracellular matrix (ECM) degradation and inflammation, which is involved with pathological microenvironmental alterations induced by damaged chondrocytes. However, current therapies are not effective in alleviating the progression of OA. Isoquercetin is a natural flavonoid glycoside compound that has various pharmacological effects including anticancer, anti-diabetes and blood lipid regulation. Previous evidence suggests that isoquercetin has anti-inflammatory properties in various diseases, but its effect on OA has not been investigated yet. In this study, through western bolt, qRT-PCR and ELISA, it was found that isoquercetin could reduce the increase of ADAMTS5, MMP13, COX-2, iNOS and IL-6 induced by IL-1β, suggesting that isoquercetin could inhibit the inflammation and ECM degradation of chondrocytes. Through nuclear-plasma separation technique, western blot and immunocytochemistry, it can be found that Nrf2 and NF-κB pathways are activated in this process, and isoquercetin may rely on this process to play its protective role. In vivo, the results of X-ray and SO staining show that intra-articular injection of isoquercetin reduces the degradation of cartilage in the mouse OA model. In conclusion, the present work suggests that isoquercetin may benefit chondrocytes by regulating the Nrf2/NF-κB signaling axis, which supports isoquercetin as a potential drug for the treatment of OA.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fucoxanthin Attenuates Myocardial Ischemia/Reperfusion-Induced Injury via AMPK/GSK-3β/Nrf2 Axis","authors":"Qianrong Zhang,&nbsp;Aiping Jin,&nbsp;Haijuan Cheng,&nbsp;Shulin Li,&nbsp;Wei Li","doi":"10.1111/cbdd.14621","DOIUrl":"https://doi.org/10.1111/cbdd.14621","url":null,"abstract":"<div>\u0000 \u0000 <p>Fucoxanthin (Fx), a xanthophyll carotenoid abundant in brown algae, possesses several biological functions, such as antioxidant, anti-inflammatory, and cardiac-protective activities. However, the role of Fx in myocardial ischemia/reperfusion (MI/R) is still unclear. Thus, the aim of this study was to investigate the effect of Fx on MI/R-induced injury and explore the underlying mechanisms. Our results showed that in vitro, Fx treatment significantly suppressed inflammatory response, oxidative stress, and apoptosis in rat cardiomyocytes exposed to hypoxia/reoxygenation (H/R). In addition, Fx led to increased phosphorylation of AMPK, AKT, and GSK-3β, and enhanced activation of Nrf2 in cardiomyocytes under H/R conditions. Notably, pretreatment with Compound C (AMPK inhibitor), partially reduced the beneficial effects of Fx in cardiomyocytes exposed to H/R. In vivo, Fx ameliorated myocardial damage, inhibited inflammatory response, oxidative stress, and apoptosis, and activated the AMPK/GSK-3β/Nrf2 signaling in myocardial tissues in MI/R rat model. Taken together, these findings indicated that Fx attenuates MI/R-induced injury by inhibiting oxidative stress, inflammatory response, and apoptosis. The AMPK/GSK-3β/Nrf2 pathway is involved in the cardioprotective effect of Fx in MI/R injury. Thus, Fx may be a promising drug for the treatment of MI/R.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142165555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinacoside Alleviates Carbon Tetrachloride-Induced Chronic Liver Injury by Modulating the NF-κB/NLRP3 Inflammasome Pathway","authors":"Ye-jun Yang,&nbsp;Juan Liu","doi":"10.1111/cbdd.14616","DOIUrl":"10.1111/cbdd.14616","url":null,"abstract":"<div>\u0000 \u0000 <p>The purpose of this study was to investigate the protective effect of echinacoside (Ech) on carbon tetrachloride (CCL4)-induced chronic liver injury in rats and its potential mechanisms. Thirty Sprague–Dawley (SD) rats were randomly divided into five groups: the Control group, the CCL4 group, the CCL4 + Ech 25 mg/kg group, the CCL4 + Ech 50 mg/kg group, and the CCL4 + Ech 100 mg/kg group. The rats were injected intraperitoneally with CCL4 solution twice a week to induce chronic liver injury, and Ech intervention lasted for 4 weeks. After the intervention, the liver and blood samples from rats were collected for subsequent analysis. Ech effectively reduced the levels of serum liver injury markers (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, alkaline phosphatase, and total bilirubin), attenuated the hepatocyte degeneration and necrosis, improved the severity of liver fibrosis, and inhibited the local inflammatory response of the liver in a dose-dependent manner. Ech effectively mitigated CCL4-induced chronic liver injury in rats by downregulating the NF-κB/NLRP3 inflammasome pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Plumbagin's Antiproliferative Mechanism in Human Cancer Cells: A Copper-Dependent Cytotoxic Approach","authors":"","doi":"10.1111/cbdd.14622","DOIUrl":"10.1111/cbdd.14622","url":null,"abstract":"<p>El Oirdi, M. 2024. “Plumbagin's Antiproliferative Mechanism in Human Cancer Cells: A Copper-Dependent Cytotoxic Approach.” <i>Chemical Biology &amp; Drug Design</i> 104: e14606.</p><p>The funding information for this article was inadvertently omitted. The correct details are included below.</p><p>This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia. Grant Number KFU241478.</p><p>We apologize for this error.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cbdd.14622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mycobacterium tuberculosis Cell Wall: An Alluring Drug Target for Developing Newer Anti-TB Drugs—A Perspective","authors":"Monica Chauhan,&nbsp;Rahul Barot,&nbsp;Rasana Yadav,&nbsp;Karan Joshi,&nbsp;Sadaf Mirza,&nbsp;Rupesh Chikhale,&nbsp;Vijay Kumar Srivastava,&nbsp;Mange Ram Yadav,&nbsp;Prashant R. Murumkar","doi":"10.1111/cbdd.14612","DOIUrl":"10.1111/cbdd.14612","url":null,"abstract":"<div>\u0000 \u0000 <p>The <i>Mycobacterium</i> cell wall is a capsule-like structure comprising of various layers of biomolecules such as mycolic acid, peptidoglycans, and arabinogalactans, which provide the Mycobacteria a sort of cellular shield. Drugs like isoniazid, ethambutol, cycloserine, delamanid, and pretomanid inhibit cell wall synthesis by inhibiting one or the other enzymes involved in cell wall synthesis. Many enzymes present across these layers serve as potential targets for the design and development of newer anti-TB drugs. Some of these targets are currently being exploited as the most druggable targets like DprE1, InhA, and MmpL3. Many of the anti-TB agents present in clinical trials inhibit cell wall synthesis. The present article covers a systematic perspective of developing cell wall inhibitors targeting various enzymes involved in cell wall biosynthesis as potential drug candidates for treating <i>Mtb</i> infection.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidation of the Microwave-Assisted Synthesis and Characterization of Heteronuclear Complexes of Bisbenzimidazole Derivatives and Their Biological Activities by In Vitro and In Silico Assays","authors":"Esra Kaplan,&nbsp;Ziya Erdem Koc,&nbsp;Ahmet Uysal,&nbsp;Abdullahi Ibrahim Uba,&nbsp;Gokhan Zengin","doi":"10.1111/cbdd.14605","DOIUrl":"10.1111/cbdd.14605","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;p&gt;A novel and efficient protocol for the microwave-assisted synthesis of diversely substituted 2,2′-bisbenzimidazol-5,6′-dicarboxylic acid (BIMCA) from the reaction of 3,4-diaminobenzoic acid with oxalic acid has been developed, which proceeds through sequential nucleophilic addition and electrophilic substitution in accordance with the Philips method. The synthetic utility of this strategy was demonstrated by the concise, one-pot synthesis of (BIMCA) and metal complexes. (BIMCA) with a [{Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;O] Schiff base ligand complex and new benzimidazole coordination compounds with double oxygen [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;] ligand complexes were obtained. The resulting [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;] ligand complex was then synthesized from Co(CH&lt;sub&gt;3&lt;/sub&gt;COO)&lt;sub&gt;2&lt;/sub&gt;.4H&lt;sub&gt;2&lt;/sub&gt;O, Ni(CH&lt;sub&gt;3&lt;/sub&gt;COO)&lt;sub&gt;2&lt;/sub&gt;.4H&lt;sub&gt;2&lt;/sub&gt;O and Cu(CH&lt;sub&gt;3&lt;/sub&gt;COO)&lt;sub&gt;2&lt;/sub&gt;.H&lt;sub&gt;2&lt;/sub&gt;O heteronuclear complexes. The condensations proceed with good yield to give products that, in certain instances, are not readily attainable by conventional condensation techniques. The structures of the compounds were identified by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (&lt;sup&gt;1&lt;/sup&gt;H NMR), elemental analysis and magnetic susceptibility. The mutagenic potential of the synthesized chemicals was evaluated by the Ames test towards mutant &lt;i&gt;Salmonella typhimurium&lt;/i&gt; strains TA98 and TA100. It was recorded that these chemicals had no mutagenic action. Also, antimicrobial activities were screened by broth microdilution test. It was seen that the minimum inhibitory concentration (MIC) against &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt;, &lt;i&gt;Staphylococcus aureus&lt;/i&gt; and &lt;i&gt;Staphylococcus epidermidis&lt;/i&gt; was 0.195 mg/mL, followed by a MIC value of 0.390 mg/mL against &lt;i&gt;Escherichia coli&lt;/i&gt; and &lt;i&gt;Salmonella typhimurium&lt;/i&gt;. [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;Co(II)] demonstrated significant antimicrobial activity against &lt;i&gt;Proteus mirabilis&lt;/i&gt; and &lt;i&gt;Staphylococcus aureus&lt;/i&gt;, with an MIC of 0.195 mg/mL, followed by an MIC of 0.390 mg/mL against &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;, &lt;i&gt;K. pneumonia&lt;/i&gt; and &lt;i&gt;Salmonella typhimurium&lt;/i&gt;. The antioxidant properties were examined using various chemical assays, and [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;O] and (BIMCA) exhibited greater 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, when compared with other compounds. Enzyme inhibitory effects were tested against acetylcholinesterase (AChE), amylase, butyrylcholinesterase (BChE) and tyrosinase. [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;Cu(II)] displayed the best AChE (IC&lt;sub&gt;50&lt;/sub&gt; 0.51 mg/mL), BChE (IC&lt;sub&gt;50&lt;/sub&gt; 0.51 mg/mL) and tyrosinase (IC&lt;sub&gt;50&lt;/sub&gt; 1.52 mg/mL) inhibitory effects. Furthermore, molecular docking calculations were performed to gain insights into the interaction between [(BIMCA){Fe(salen)}&lt;sub&gt;2&lt;/sub&gt;] and AChE, and between [","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of PD-1 in Skin Cancer: Molecular Mechanism, Clinical Applications, and Resistance","authors":"Neha Sharma,&nbsp;Rupa Mazumder,&nbsp;Pallavi Rai,&nbsp;Abhijit Debnath","doi":"10.1111/cbdd.14613","DOIUrl":"10.1111/cbdd.14613","url":null,"abstract":"<div>\u0000 \u0000 <p>Skin cancer is a widespread worldwide health concern, manifesting in many subtypes such as squamous cell carcinoma, basal cell carcinoma, and melanoma. Although all these types occur frequently, they generally lack the possibility of being cured, emphasizing the importance of early discovery and treatment. This comprehensive study explores the role of programmed cell death protein 1 (PD-1) in skin cancer, focusing on its molecular mechanisms in immune regulation and its critical role in tumor immune evasion, while also clarifying the complexities of immune checkpoints in cancer pathogenesis. It critically evaluates the clinical applications of PD-1 inhibitors, spotlighting their therapeutic potential in treating skin cancer, while also addressing the significant challenge of resistance. This work further discusses the evolution of resistance mechanisms against PD-1 inhibitors and suggests potential approaches to mitigate these issues, thereby enhancing the effectiveness of these therapies. The study further highlights the current state of PD-1 targeted therapies and sets the stage for future research aimed at optimizing these treatments for better clinical outcomes in skin cancer.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}