Anti-cancer agents in medicinal chemistry最新文献

{"title":"S4 Induces Apoptosis, Cell Cycle Arrest, and Metabolic Alterations in Breast Cancer Cells.","authors":"Mervenur Yavuz, Turan Demircan","doi":"10.2174/0118715206494213260708101802","DOIUrl":"https://doi.org/10.2174/0118715206494213260708101802","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer (BC) remains a primary driver of cancer-related mortality globally, necessitating the identification of novel molecular targets. While androgen receptor (AR) signaling is a recognized modulator of breast oncology, the therapeutic efficacy of selective androgen receptor modulators (SARMs), particularly S4 (Andarine), remains poorly characterized in this context.</p><p><strong>Methods: </strong>The anti-cancer activity of S4 was investigated across Estrogen Receptor-positive (MCF-7) and Triple- Negative (MDA-MB-231) models. Cellular viability, clonogenicity, and migratory capacity were assessed, alongside flow cytometric analysis of apoptosis and cell cycle distribution. Mechanistic insights were derived from quantitative gene expression profiling and untargeted LC-MS-based metabolomics.</p><p><strong>Results: </strong>S4 treatment induced a significant, dose-dependent reduction in cellular viability, suppressed clonogenicity and migration, and promoted apoptosis and cell cycle arrest, with MCF-7 cells exhibiting S-phase arrest and MDA-MB-231 cells exhibiting G0/G1-S arrest. Gene expression analysis revealed modulation of genes associated with apoptosis, stress response, and cell-cycle regulation, supporting the anti-cancer effects of S4. Metabolomic analysis further demonstrated that S4 exposure leads to marked remodeling of metabolic pathways associated with amino acid turnover, nucleotide homeostasis, lipid metabolism, and cofactor utilization.</p><p><strong>Discussion: </strong>These alterations point to a coordinated yet context-dependent metabolic response, characterized by shared core changes alongside distinct subtype-specific adaptations. Our findings suggest that S4 treatment is associated with significant alterations in breast cancer growth and metabolic pathways.</p><p><strong>Conclusion: </strong>The subtype-specific metabolic rewiring suggests that S4 exploits unique metabolic vulnerabilities, supporting further investigation of SARMs in breast cancer models.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808130","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":"Gelatin Nanocarriers as Biocompatible Platforms for Targeted Drug Delivery in Cancer Therapy.","authors":"Lalit Kumar, Vikas Aggarwal, Komal Komal, Neelam Sharma, Swati Kashyap, Saurabh Sharma, Mridhula Manimaran","doi":"10.2174/0118715206433103251215092013","DOIUrl":"https://doi.org/10.2174/0118715206433103251215092013","url":null,"abstract":"<p><strong>Introduction: </strong>Innovative drug delivery systems are required to improve the therapeutic efficacy of cancer, which continues to be a global health challenge. Gelatin-based nanocarriers provide a prospective platform for targeted cancer therapy by utilizing their biocompatibility and stimuli-responsive properties, thereby addressing the limitations of conventional treatments.</p><p><strong>Methods: </strong>This review provides an overview of gelatin nanoparticles for the effective delivery of anticancer drugs. Various search databases were utilized for literature investigation, including PubMed, ScienceDirect, and Google Scholar. All the studies from the year 2015 to 2025 were added, along with patents associated with the field.</p><p><strong>Results: </strong>In lung, breast, melanoma, and other miscellaneous malignancies, gelatin nanoparticles exhibit reduced systemic toxicity and improved drug targeting. When combined with therapies, such as ultrasound or photothermal treatment, studies have demonstrated enhanced cellular absorption, sustained drug release, and synergistic effects. The increasing interest in their diagnostic and therapeutic applications is reflected in patents.</p><p><strong>Discussion: </strong>The improved treatment outcomes are facilitated by the versatility of gelatin nanocarriers, which allows for the tailored release of drugs in response to tumor-specific stimuli. Nevertheless, clinical implementation is impeded by obstacles, such as scalable production, nanoparticle stability, and unpredictable drug release. To surmount these obstacles, there are emerging strategies, such as stimuli-responsive and size-transformable nanoparticles.</p><p><strong>Conclusion: </strong>The precise delivery of drugs through gelatin-based nanosystems has the potential to revolutionise cancer therapy. To ensure their successful clinical application, it is essential to address current limitations through innovative engineering and integration with advanced therapeutic modalities.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705085","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":"Chemopreventive Effects of Boldine and Naringenin on DMH-Induced Colorectal Carcinogenesis.","authors":"Monu Kumar Kashyap, Akash Ved, Pranay Wal, Akhand Pratap Singh","doi":"10.2174/0118715206432112260624054115","DOIUrl":"https://doi.org/10.2174/0118715206432112260624054115","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer causes high global mortality. Natural compounds boldine and naringenin exhibit preventive potential by reducing oxidative stress, inhibiting cell proliferation, and regulating inflammation, making them promising, safer therapeutic agents. This study evaluated the chemopreventive potential of boldine and naringenin using DMH-induced Wistar rats, in silico EGFR binding studies, and in vitro antiproliferative assays.</p><p><strong>Methods: </strong>A multi-pronged approach was employed to evaluate the chemopreventive potential of boldine and naringenin. In silico molecular docking and dynamics simulations assessed binding affinity and stability with EGFR kinase, a key regulator of cancer progression. In vitro studies evaluated cytotoxicity in HCT116 colorectal cancer (CRC) cells using the MTT assay, and antioxidant activity was measured using the DPPH assay. In vivo, Wistar rats were divided into five groups: Control, DMH only, DMH + Boldine, DMH + Naringenin, and DMH + Vincristine. Lipid profiles, oxidative stress markers, and colon histopathology were analyzed.</p><p><strong>Results: </strong>Molecular docking revealed boldine's stronger binding affinity (-8.75 kcal/mol) to EGFR kinase compared to naringenin (-7.43 kcal/mol), with dynamics simulations confirming stable interactions beyond 100 ns. In vitro, both compounds significantly reduced HCT116 cell proliferation dose-dependently and exhibited robust antioxidant activity in the DPPH assay. In vivo, boldine and naringenin counteracted DMH-induced lipid imbalances (by reducing serum cholesterol, LDL, VLDL, and TG levels, with a simultaneous increase in HDL) and modulated oxidative stress (by decreasing malondialdehyde and restoring glutathione, superoxide dismutase, and catalase levels; p<0.05). Histopathological analysis showed that both compounds, restoring nearnormal colon architecture, markedly alleviated DMH-induced hyperplastic polyps and crypt distortions.</p><p><strong>Discussion: </strong>Boldine and naringenin demonstrated chemopreventive potential by regulating lipid metabolism, bolstering antioxidant defenses, and preserving colon tissue integrity. Their strong EGFR interactions suggest utility as complementary therapies in CRC management, though further clinical validation is required to confirm their therapeutic potential.</p><p><strong>Conclusion: </strong>Boldine and naringenin effectively attenuated DMH-induced colorectal carcinogenesis by modulating lipid profiles, reducing oxidative stress, and mitigating histological abnormalities. Their multifaceted mechanisms highlight their promise as adjuvant therapies for CRC, necessitating further clinical studies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705117","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":"In Vitro and In Vivo Evaluation of Cytotoxic and Genotoxic Potentials of Martynia annua-Derived Chitosan Nanoparticles Toward Potential Anticancer Application.","authors":"Narayanasamy Duraisamy, Sangeetha Dhayalan, Geetha Mani, Rajalakshmi Govindaraju, Brindha Ganesan, Mukul Machhindra Barwant, Adil Abalkhail, Suresh Babu Kondaveeti, Rashmi Pathak, Syed Ahmed Hussain","doi":"10.2174/0118715206455401260302055629","DOIUrl":"https://doi.org/10.2174/0118715206455401260302055629","url":null,"abstract":"<p><strong>Introduction: </strong>Chitosan Nanoparticles (CNPs), derived from the natural polymer chitosan, are increasingly recognized as highly versatile nanocarriers for delivering biological macromolecules in biomedical and biotechnological applications. Their utility in fields such as drug delivery, gene therapy, and tissue engineering is highly valued for their biocompatibility, biodegradability, and targeted delivery capabilities. However, comprehensive safety evaluations, including cytotoxicity and genotoxicity, are crucial before clinical or experimental applications. Green synthesis using plant extracts offers an eco-friendly route for nanoparticle production and may enhance biocompatibility. In this study, Martynia annua was employed, a plant with bioactive properties, to synthesize CNPs and evaluate their safety in vitro and in vivo.</p><p><strong>Materials and methods: </strong>CNPs were synthesized using an aqueous extract of Martynia annua via ionic gelation. Cytotoxicity was assessed in CHO-K1 cells using the chromosomal aberration assay across concentrations up to 2000 μg/mL. Genotoxic effects were evaluated in murine models using the micronucleus test at doses up to 2000 mg/kg. Standard controls were included to validate the assays.</p><p><strong>Results: </strong>The CNPs demonstrated uniform morphology and nanoscale size. No significant cytotoxicity was observed in CHO-K1 cells, and chromosomal aberrations remained within baseline levels. Similarly, the in vivo micronucleus test showed no increase in micronuclei formation, indicating the absence of genotoxic effects even at high doses.</p><p><strong>Discussion: </strong>These findings suggest that Martynia annua-derived CNPs are biocompatible and safe for cellular and systemic exposure. The green synthesis approach may further reduce the potential toxicity associated with chemical reagents.</p><p><strong>Conclusion: </strong>Naturally synthesized CNPs from Martynia annua are safe, non-cytotoxic, and non-genotoxic, supporting their potential application as nanocarriers for biological macromolecule delivery in therapeutic and biotechnological contexts.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148705130","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":"Dendritic Cell Vaccines for Glioblastoma: A Systematic Review and Meta-Analysis Comparing New-Onset and Recurrent Cases.","authors":"Abdulsalam Mohammed Aleid, Ibrahim Abdullah Houlbah, Mohammed Yahya Abutaleb, Mazen Mohammed Hakami, Faisal Ali M Alshahrani, Saad Khalid Aldawsari, Rafaa Ahmed Salem Algethmi, Alaa Abdulrahman Ismail, Sami Fadhel Almalki","doi":"10.2174/0118715206406017251124090916","DOIUrl":"https://doi.org/10.2174/0118715206406017251124090916","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma (GBM), an aggressive and highly recurrent brain tumor, remains a significant challenge despite advancements in treatment. With a median survival of only 15 months and recurrence often occurring within a year despite aggressive initial therapy, there is an urgent need for more effective therapeutic strategies. The interplay of intrinsic and extrinsic factors, such as genetic mutations and alterations in the tumor microenvironment, drives recurrence, highlighting the importance of targeted approaches. Emerging therapies, particularly dendritic cell (DC)-based immunotherapies, show promise in enhancing anti-tumor immune responses. This study aimed to compare the effectiveness of DC-based immunotherapy in improving survival outcomes for patients with newly diagnosed or recurrent GBM.</p><p><strong>Methods: </strong>We conducted a comprehensive search across four electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Scopus, and Web of Science) up to March 2024 to identify pertinent studies evaluating the efficacy of DC vaccines in the treatment of both newly diagnosed and recurrent GBM. The quality of evidence from trials was assessed using the Cochrane risk-of-bias version 1 (RoB1) tool. Data from the included studies were extracted into a standardized online sheet and analyzed using Review Manager (RevMan) 5.4.</p><p><strong>Results: </strong>Our search identified three records with a total of 355 patients. The results of the meta-analysis showed that DC-based immunotherapy had a greater impact on recurrent GBM than on newly diagnosed GBM. However, overall survival favored newly diagnosed cases, demonstrating a more protective effect (HR = 0.62, 95% confidence intervals (CI) (0.46,0.84), p = 0.002) with no significant heterogeneity (p = 0.97, I2 = 0%). A similar trend was observed for progression-free survival, favoring newly diagnosed cases over recurrent ones (HR = 0.56, 95% CI (0.31,1.00), p = 0.05), with no significant heterogeneity (p = 0.48, I2 = 0%). Moreover, comparable results were observed for survival at both 12 and 24 months.</p><p><strong>Conclusion: </strong>Dendritic cell-based immunotherapy can enhance survival outcomes in GBM patients. The results showed DC-based immunotherapy to be more effective in newly diagnosed GBM than in recurrent cases.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683464","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":"Emrelis for c-Met Positive NSCLC: A Breakthrough in Antibody-Drug Conjugate-based Treatment Approved by the FDA.","authors":"Sayan Samui, Aman Kumar, Preeti Patel, Balak Das Kurmi","doi":"10.2174/0118715206446635251226113107","DOIUrl":"https://doi.org/10.2174/0118715206446635251226113107","url":null,"abstract":"<p><p>Telisotuzumab Vedotin (Teliso-V), previously known as ABBV-399, is a novel, first-in-class antibodydrug conjugate developed by AbbVie. It combines an anti-c-Met monoclonal antibody (ABT-700) with monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent, via a cleavable linker. This design allows selective delivery of the cytotoxic payload to c-Met-overexpressing tumour cells, thereby bypassing reliance on MET signalling for efficacy. Preclinical studies demonstrated that ABBV-399 effectively inhibited the growth of xenograft tumors refractory to other MET-targeted inhibitors. In early Phase I trials, the agent showed a favourable safety profile and elicited objective tumour responses in c-Met-expressing non-small cell lung cancer (NSCLC) patients. In the Phase II LUMINOSITY study, which served as the basis for accelerated FDA approval, Teliso-V demonstrated an overall response rate (ORR) of 35% and a median duration of response (DOR) of 9 months in patients with high c-Met protein overexpression. Continued approval may depend on confirmatory Phase III data.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597867","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":"Rechallenge Therapy: New Dimensions in Cancer Therapy.","authors":"Himanshu Singh, Rajnish Kumar, Avijit Mazumder, Ranjeet Kumar Yadav","doi":"10.2174/0118715206402851251203225833","DOIUrl":"https://doi.org/10.2174/0118715206402851251203225833","url":null,"abstract":"<p><strong>Introduction: </strong>The evolution of resistance to different types of cancer therapies has become a significant challenge in oncology research, leading to disease progression and limited treatment options. Rechallenge therapy, where a previously used treatment is reintroduced after a period of discontinuation, has emerged as a potential strategy to overcome resistance.</p><p><strong>Methods: </strong>This review synthesizes current knowledge on rechallenge therapy by analyzing data from clinical trials, retrospective studies, and case reports. A comprehensive examination was conducted across multiple cancer types and therapeutic classes, including immunotherapy, chemotherapy, targeted therapy, hormonal therapy, and combination approaches.</p><p><strong>Results: </strong>The efficacy of rechallenge therapy varies across cancer types. For instance, in metastatic colorectal cancer, anti-EGFR rechallenge therapy has shown response rates of 20-30% in RAS wild-type patients after a drug-free interval. In prostate cancer, rechallenge with androgen deprivation therapy or abiraterone has demonstrated biochemical response rates of approximately 30-40% in selected populations.</p><p><strong>Discussion: </strong>In hormone receptor-positive breast cancer, endocrine therapy rechallenges, especially following a treatment break, have yielded clinical benefit rates of over 40% in some cohorts. These outcomes are influenced by tumor biology, duration of prior response, molecular profiling, and patient selection criteria.</p><p><strong>Conclusion: </strong>Rechallenge approaches show promise as viable options for treating cancer recurrence and resistance, but their application must be carefully tailored to each patient. A well-planned scientific strategy is required to optimize different rechallenge approaches, identify predictive biomarkers, and understand the longterm outcomes associated with this method.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597857","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":"Lazertinib: A Selective EGFR Mutant Inhibitor to Treat Non-Small Cell Lung Cancer.","authors":"Hyma Mandapaka, Surya Kanta De","doi":"10.2174/0118715206446336251226053220","DOIUrl":"https://doi.org/10.2174/0118715206446336251226053220","url":null,"abstract":"<p><p>One of the leading causes of death related to cancer worldwide is non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are one of the most important therapeutic targets. Lazertinib is an irreversible EGFR tyrosine kinase inhibitor (TKI) that is selectively active against EGFR mutations and the T790M resistance mutation, but not against wild-type EGFR. In this paper, we have evaluated the significant role of lazertinib in the treatment of NSCLC, compared with agents, such as osimertinib. We have analyzed the pharmacological benefits, clinical trial evidence, and interactions with the central nervous system (CNS), as well as its active role in first-line therapy beyond acquired resistance. The early-phase results are promising, but queries regarding resistance mechanisms and treatment protocols remain. We have conducted a detailed investigation of lazertinib's therapeutic properties, its role in combination therapies, and its potential to improve treatment outcomes in EGFR-mutant NSCLC. We aimed to highlight both the opportunities and clinical uncertainties associated with lazertinib in cancer care.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597850","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":"CD147 Is Involved in Tanshinone IIA-Induced Reprogramming of the Warburg Effect in Prostate Cancer Cells.","authors":"Yunye Wang, Jierui Zhao, Shutong Chen, Cheng Hu, Jing Guo, He Wang, Lichun Xing, Xingyu Zhao, Ruowen Zhang, Wei Zhang","doi":"10.2174/0118715206482095260702175848","DOIUrl":"https://doi.org/10.2174/0118715206482095260702175848","url":null,"abstract":"<p><strong>Introduction: </strong>Cancer cells exhibit metabolic characteristics known as the Warburg effect, which is aerobic glycolysis. Tan IIA, a compound from Salvia miltiorrhiza, has antitumor effects, but its impact on prostate cancer metabolism is not fully understood.</p><p><strong>Methods: </strong>The effects of Tan IIA on prostate cancer cell proliferation and apoptosis were assessed. Glucose metabolism was evaluated by measuring glycolysis-related metabolic changes and the expression levels of key metabolic enzymes. The underlying molecular mechanisms were investigated by analyzing the AKT/mTOR/ HIF-1α signaling pathway and the role of CD147.</p><p><strong>Results: </strong>Tan IIA significantly suppressed prostate cancer cell proliferation and induced apoptosis by inhibiting glucose metabolism. Treatment with Tan IIA downregulated hypoxia-inducible factor-1α (HIF-1α) expression via blockade of the AKT/mTOR signaling cascade. This resulted in reduced expression levels of critical glycolytic regulators, including glucose transporter 1 (GLUT1), pyruvate kinase M2 (PKM2), and hexokinase 2 (HK2). Furthermore, CD147 silencing impaired glycolysis, an effect potentiated by Tan IIA, suggesting a mechanism involving CD147 inhibition.</p><p><strong>Discussion: </strong>Tan IIA disrupts the glycolytic pathway in prostate cancer cells by suppressing the activity of the AKT/mTOR/HIF-1α axis and potentially through CD147 modulation Conclusion: In summary, these results establish Tan IIA as a potential antitumor compound worthy of further preclinical investigation that exerts its antitumor activity by targeting the unique metabolic dependencies of prostate cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597906","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":"CDK4/6-Based Drug Research and Development: A Four-Year Update.","authors":"Miao-Xia Pu, Wen-Bo Xu, Li Ding, Shuang-Shuang Zhang, Luan-Yuan Tian, Shuang-Xi Gu","doi":"10.2174/0118715206469469260705112718","DOIUrl":"https://doi.org/10.2174/0118715206469469260705112718","url":null,"abstract":"<p><strong>Introduction: </strong>CDK4/6 kinases are crucial cell cycle regulators, and pharmacological inhibition of these kinases to block the G1-to-S phase transition has become an integral part of modern cancer therapy. Although five CDK4/6 inhibitors have been clinically approved, the development of acquired drug resistance greatly limits their long-term therapeutic efficacy.</p><p><strong>Methods: </strong>This review systematically summarizes the latest advances in CDK4/6 inhibitor research from 2022 to 2025, focusing on their structural features, biological functions, and preclinical research progress. In addition, this article comprehensively explores emerging therapeutic strategies, including bifunctional molecules and PROTAC-based protein degraders.</p><p><strong>Results: </strong>The action mechanisms of conventional CDK4/6 inhibitors have been relatively well elucidated. Notably, these emerging strategies have yielded encouraging preclinical results, including co-targeting CDK4/6 with other critical therapeutic nodes (e.g., HDAC, PARP1) and adopting PROTAC-based degraders to directly induce the degradation of target proteins. A growing number of innovative approaches targeting drug resistance via multi-target inhibition and induced protein degradation have been developed. Distinct from classical singletarget monotherapy, these innovative strategies leverage distinct pharmacological pathways, offering feasible research directions to improve therapeutic efficacy and delay drug resistance.</p><p><strong>Discussion: </strong>In-depth understanding of CDK4/6 inhibitors and the continuous development of bifunctional agents and protein degraders provides key theoretical and technical support for the design of next-generation therapeutic strategies to address current clinical limitations. These research advances are expected to facilitate the development of more effective and long-lasting therapeutic modalities for tumor treatment.</p><p><strong>Conclusion: </strong>This review summarizes recent advances in CDK4/6 inhibitors. Novel dual-target and PROTACbased strategies offer promising resistance-overcoming tumor therapies.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597838","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}