Anti-cancer Agents In Medicinal Chemistry[JOURNAL]
Sun
200 papers
An Updated Insight into the Phytomolecules Reported for the Treatment of Colon Cancer from 2015 to 2024.
Nooreen Z, Rai AK, Jaisal P … +2 more , Tandon S, Tiwari K
Anticancer Agents Med Chem · 2026 Jan · PMID 41582379 · Publisher ↗
INTRODUCTION: During the last 20 years, the prevalence of colon cancer, among the most prevalent gastrointestinal cancers globally, has increased in the majority of nations. The current review compiled phytochemicals rep...
INTRODUCTION: During the last 20 years, the prevalence of colon cancer, among the most prevalent gastrointestinal cancers globally, has increased in the majority of nations. The current review compiled phytochemicals reported to manage colon cancer from 2015 to 2020. METHODS: The article is taken from various sources of Web of Science, PubMed, Google Scholar, Scopus, Elsevier, Research Gate, and PubChem Results: Colon cancer is the leading cause of cancer-related death worldwide and impacts both men and women. Because of the present dietary habits and lifestyle, which include eating a lot of meat, drinking alcohol, and not exercising enough, the death rate from colon cancer has increased globally. A robust gastrointestinal tract and the control of regular intestinal activity seem to be significantly influenced by dietary fiber. DISCUSSION: The prognosis for colon cancer is dismal, as it is frequently discovered at an advanced stage. Despite some evidence suggesting a diet low in fibre predisposes to colon carcinogenesis. The use of phytochemicals may help in the management of colon cancer. CONCLUSION: By altering many signalling pathways involved in the control of chronic inflammation, the cell cycle, autophagy, apoptotic metastasis, and angiogenesis, these natural compounds have been shown to have anticolon cancer properties. Compounds such as Ellagitannin, Ursolic acid, Garcinol, Oxymatrine, Emodin, Catalpol, Resveratrol, Zerumbone, Curcumin, Pyrogallol, α-Hederin, Juglone, Zingerone, Brosimone I, Organosilicon, Myricetin, Tenacissoside H, 6,8-Diprenylorobol, Plumbagin, Dioscin, and many more are listed with their mechanisms of action.
Design, Synthesis, Bioactivity, and Docking Studies of Isatin-Hydrazone Derivatives as Potential CDK-2 Inhibitors.
Tao Y, Guo K, Liao X … +1 more , Yan G
Anticancer Agents Med Chem · 2026 Jan · PMID 41582378 · Publisher ↗
INTRODUCTION: Isatin derivatives are an important class of nitrogen-containing heterocyclic compounds that have exhibited a broad spectrum of pharmacological and biological activities. The condensation reaction of isatin...
INTRODUCTION: Isatin derivatives are an important class of nitrogen-containing heterocyclic compounds that have exhibited a broad spectrum of pharmacological and biological activities. The condensation reaction of isatin readily forms C=N-bonded compounds due to the high reactivity of the 3-position carbonyl group. Hydrazone compounds also play an important role in research related to pesticide chemistry and medicinal chemistry. Therefore, we propose that the compound incorporates both indigo and hydrazone skeletons, which could confer excellent biological activity. The objective of this study is to synthesize novel isatinhydrazone derivatives that function as CDK2 inhibitors through molecular docking and bioactivity studies. METHODS: A series of isatin-hydrazone derivatives was synthesized and characterized using H NMR, C NMR, and HRMS. The in vitro cytotoxicities of these compounds were assessed using an MTT assay against A549 (non-small cell lung cancer), HepG2 (hepatocellular carcinoma), and HeLa (cervical cancer) cell lines. RESULTS: According to the results of the MTT assay, compounds 2e and 2f exhibited potent selectivity and activity against A549 (IC = 5 nM) and HeLa cells (IC = 6 nM), respectively. Compound 2h demonstrated dual efficacy against A549 (IC= 8 nM) and HepG2 (IC= 13 nM). In addition, molecular docking revealed strong binding affinities and stable interactions between active derivatives and key residues within the CDK2 active site. CONCLUSION: These novel isatin-hydrazone derivatives, particularly 2e, 2f, and 2h, could be used as potential anticancer agents that inhibit CDK2 kinase activity.
Traditional and Sustainable Methods for the Synthesis of Quinoline Derivatives as Anticancer Agents (2019-Present): A Comprehensive Review.
Thakur GS, Gupta AK, Vaishnav Y … +2 more , Annadurai S, Jain SK
Anticancer Agents Med Chem · 2026 · PMID 41572702 · Full text
INTRODUCTION: Heterocyclic compounds are widely utilized in the development of anticancer medications due to their diverse structures and ability to interact with multiple biological targets within cancer cells. Quinolin...
INTRODUCTION: Heterocyclic compounds are widely utilized in the development of anticancer medications due to their diverse structures and ability to interact with multiple biological targets within cancer cells. Quinoline is a heterocyclic compound and an essential compound in the domains of industrial and pharmaceutical chemistry because of its various pharmacological effects. Researchers are developing new traditional, synthetic, and innovative green approaches to synthesize mono- or poly-substituted quinoline derivatives for anticancer activity. METHODS: A comprehensive literature survey was conducted using multiple databases, including Google Scholar, PubMed, SpringerLink, ScienceDirect, and others, to investigate the existing literature on synthetic strategies for various quinoline derivatives. This review article intends to present a summary of various traditional synthetic methods alongside innovative green approaches. RESULTS: Many researchers have demonstrated that quinoline derivatives can be synthesized using various methods, including traditional techniques, hybrid approaches with heterocyclic structures, and innovative green synthetic methods, as well as elucidating their structure-activity relationships for potential use as anticancer agents. The majority of traditional synthetic methods rely on hazardous chemicals, low reaction rates, high temperatures, and high pressures. Currently, the green chemistry approach produces eco-friendly, economical, highyield, pure, and outstanding products in the fields of industry and pharmaceuticals. DISCUSSION: This section explores various affordable and eco-friendly synthetic techniques that produce potent and specific quinoline compounds, intended for use as anticancer agents. CONCLUSION: The progress demonstrated in the green synthetic methods and the development of quinoline-based compounds as new treatment options could aid in identifying new and effective quinoline derivatives for cancer treatment in the future.
Disrupting Cancer Pathways with Nanogel-Encapsulated Wheatgrass Phytopharmaceuticals for Skin Cancer Therapy.
Singh D, Singh AP, Gupta R
Anticancer Agents Med Chem · 2026 Jan · PMID 41572701 · Publisher ↗
INTRODUCTION: Skin cancer is a major global health concern, with rising prevalence and limited effectiveness of conventional therapies. Natural phytopharmaceuticals, particularly those derived from Triticum aestivum (whe...
INTRODUCTION: Skin cancer is a major global health concern, with rising prevalence and limited effectiveness of conventional therapies. Natural phytopharmaceuticals, particularly those derived from Triticum aestivum (wheatgrass), offer promising therapeutic potential due to their antioxidant, anti-inflammatory, and anticancer properties. This review explores the potential of nanogel-encapsulated wheatgrass bioactives to modulate molecular pathways involved in skin cancer development. METHODS: A comprehensive review was conducted of preclinical studies, advances in nanogel-based delivery systems, and the molecular pharmacology of wheatgrass phytoconstituents. Emphasis was placed on their interactions with key cancer-related signaling pathways and the impact of nanogels on pharmacokinetic and pharmacodynamic profiles. RESULTS: Wheatgrass bioactives were found to regulate oncogenic pathways, including PI3K/Akt, MAPK/ERK, NF-κB, and p53. Nanogel encapsulation enhanced solubility, stability, targeted delivery, and bioavailability. Both in vitro and in vivo studies demonstrated improved cytotoxicity against melanoma and non-melanoma skin cancer cells, with reduced off-target effects. DISCUSSION: Nanogel-based delivery of wheatgrass phytopharmaceuticals offers a multi-targeted strategy by modulating multiple cancer pathways while addressing challenges associated with natural compound delivery. Despite promising preclinical results, translational limitations remain, including scarce human trials and variability in formulation. Future research should prioritize clinical validation and regulatory standardization. CONCLUSION: Nanogel-encapsulated wheatgrass bioactives represent a novel, mechanism-driven, and targetspecific approach for skin cancer therapy, with the potential to advance phytotherapy toward mainstream oncology treatment.
Network Pharmacology Reveals Luteolin From Vitex Negundo Novel Targets CDK1/Cyclin B In ER+ Breast Cancer Stem Cells.
Basnet R, Basnet BB, Zhaojian S … +7 more , Amissah OB, Amjad N, Yusuf B, Sun Y, Huang R, Huangfang X, Li Z
Anticancer Agents Med Chem · 2026 Jan · PMID 41568514 · Publisher ↗
INTRODUCTION: Breast cancer remains a leading cause of cancer-related mortality in women, primarily due to Breast Cancer Stem Cells (BCSCs), which contribute to tumor progression, metastasis, and resistance to convention...
INTRODUCTION: Breast cancer remains a leading cause of cancer-related mortality in women, primarily due to Breast Cancer Stem Cells (BCSCs), which contribute to tumor progression, metastasis, and resistance to conventional therapies. Vitex negundo Linn. (VN), a medicinal plant abundant in polyphenolic flavonoids such as luteolin (LT), has previously demonstrated anticancer potential. This study investigates the active metabolite profiling of VN targeting BCSCs and evaluates LT's therapeutic potential through in vitro and in silico approaches. METHODS: An integrated network pharmacology and computational approach identified VN metabolites targeting BCSCs, including CDK1, cyclin B1/B2, TOP1, GSK-3β, and PARP1. Mutational analysis in MCF-7 cells followed by luteolin (LT) treatment assessed its impact on stemness, gene expression, ROS generation, cell cycle, and apoptosis. Molecular docking and dynamics confirmed LT's strong binding to CDK1/Cyclin B. RESULTS: LT significantly reduced the properties of BCSCs by inhibiting the CDK1/Cyclin B complex and downregulating associated genes. It induced ROS-mediated apoptosis and altered cell cycle distribution, notably increasing G1 and S phase populations. Molecular modeling confirmed strong binding of LT to CDK1/Cyclin B, suggesting disruption of cell cycle regulation and self-renewal. DISCUSSION: LT binds strongly to CDK1 and Cyclin B proteins, suppressing their activity in MCF-7 cells. This disrupts gene expression linked to BCSC self-renewal, induces apoptosis, and causes cell cycle arrest. LT targeting CDK1/Cyclin B complexes offers promising therapeutic potential for future clinical development against BCSCs. CONCLUSION: LT from VN shows promise as a therapeutic agent targeting CDK1/Cyclin B in ER+ breast cancer stem cells, supporting its potential for clinical development.
Discovery of Small Molecule Inhibitors against Polo-Like Kinase 1 Targeting Breast Cancer.
Munieswaran G, Manickam V
Anticancer Agents Med Chem · 2026 Jan · PMID 41540527 · Publisher ↗
INTRODUCTION: The polo-like kinase-1 (PLK1) plays a significant role in cell cycle regulation and proliferation; upon dysregulation, PLK1 activates different oncogenic pathways that lead to breast cancer. Therefore, targ...
INTRODUCTION: The polo-like kinase-1 (PLK1) plays a significant role in cell cycle regulation and proliferation; upon dysregulation, PLK1 activates different oncogenic pathways that lead to breast cancer. Therefore, targeting the PLK1 protein on the kinase domain prevents the possibility of tumor development. METHODS: A machine learning model was developed to screen small molecules against PLK1 using a cancer bioassay dataset. The binding affinity and structural integrity of the complex were assessed using molecular docking and dynamic studies. In vitro evaluation was then performed for the screened compound against the SKBR3 cell line. RESULTS: The research findings highlighted the silymarin flavonoid to have a greater binding energy with PLK1 (-9.2 Kcal/mol) than other molecules (above -8.5 Kcal/mol). Additionally, the molecular dynamics simulation showed silymarin to be more stable, less flexible, and more compact with PLK1. Further, the binding free energy revealed silymarin to be more stable with PLK1 (-13.25 kcal/mol) than volasertib (-2.87 kcal/mol). The IC50 value of silymarin was found to be 95.76 μg/mL, inducing apoptosis on the SKBR3 cell line. DISCUSSION: Despite PLK1 being predicted as a potential oncogenic target, the treatment choices were limited. A cheminformatics approach was utilized for screening inhibitors against PLK1. The in silico and in vitro evaluations indicated that silymarin effectively inhibited the PLK1 protein in breast cancer. CONCLUSION: These research findings established silymarin as a potential alternative drug targeting PLK1, which is highly expressed in HER2-positive breast cancer, and modulates the oncogenic processes not just in breast cancer, but also in other cancers.
Molecular Simulation, Pharmacophore Mapping, and 3D QSAR Modeling on Chromene-Based SERDs.
Thareja S, Bisht S
Anticancer Agents Med Chem · 2026 Jan · PMID 41510727 · Publisher ↗
INTRODUCTION: Estrogen receptor (ERα) is known to be a legitimate therapeutic target for the treatment of ER-positive breast cancer. Although selective estrogen receptor degraders (SERDs) like fulvestrant suppress ER sig...
INTRODUCTION: Estrogen receptor (ERα) is known to be a legitimate therapeutic target for the treatment of ER-positive breast cancer. Although selective estrogen receptor degraders (SERDs) like fulvestrant suppress ER signaling, their limited bioavailability challenges efficacy. Additionally, activating mutations in the ERα mediate resistance to endocrine therapy. METHODS: To elucidate the structural activity relationship within a chromene-based scaffold, we conducted pharmacophore mapping and Gaussian field-based 3D QSAR modelling. The most active analogue was docked into the ERα ligand binding domain (PDB ID: 6V8T) and then subjected to molecular dynamics simulations and molecular mechanics generalized born surface area (MM/ GBSA) binding-free energy calculations. RESULTS: The pharmacophore mapping produces a five-point hypothesis, of which HHHRR_1 achieved the highest survival score (6.423) with a fitness score close to 3. Using HHHRR_1, a Gaussian Field-based 3D QSAR model with strong internal predictivity (cross-validated q2 is 0.8) and an excellent external validation was developed (r2 is 0.94). Compound 18 demonstrated stable binding in the ERα pocket with a ΔGbind MM/GBSA value of -67.03 kcal/mol, outperforming fulvestrant with a ΔGbind MM/GBSA of -64.76 kcal/mol. These findings suggest compound 18 engages critical ERα interactions more effectively with the target. DISCUSSION: The integrated modelling approach, like pharmacophore mapping, 3D QSAR, docking, and molecular dynamics, elucidated molecular characteristics essential for potent ERα degradation. Compound 18, having superior binding affinities, implies that optimizing these features on a chromene scaffold can yield new oral SERDs with enhanced therapeutic potential. CONCLUSION: Based on the results of pharmacophore mapping, docking, molecular simulation, and 3D QSAR studies, we have designed a new set of chromene scaffold-based derivatives as potent SERDs along with their predicted activity.
Artichoke Extract Ameliorates CCl4-Induced Hepatocellular Carcinoma in Albino Rats by Regulating the Phosphatidylinositol 3-kinase/serine-threonine Protein Kinase Pathway.
Zein N, Yassin FA, M Rashad M … +2 more , Talaat E, Abd Elhameed HAH
Anticancer Agents Med Chem · 2026 Jan · PMID 41510726 · Publisher ↗
INTRODUCTION: Cynara scolymus (Artichoke) is a medicinal plant of significant pharmacological importance, rich in phenolic acids and flavonoids. Therefore, the current research aimed to assess the anticancer properties a...
INTRODUCTION: Cynara scolymus (Artichoke) is a medicinal plant of significant pharmacological importance, rich in phenolic acids and flavonoids. Therefore, the current research aimed to assess the anticancer properties and potential molecular pathways of Artichoke extract utilizing an HCC rat model induced by Carbon tetrachloride (CCl4). METHODS: Fifty male albino rats were randomly allocated into five groups: a negative control group (NCG), a positive control group (PCG), an Artichoke protective group (APG), an Artichoke treatment group (ATG), and a cisplatin treatment group (CTG). Blood and liver tissue samples were collected for biochemical and molecular analyses at the end of the experiment. We also performed histological examination of the liver and an immunohistochemistry assay for the significant tumor marker alpha-fetoprotein (AFP) and Nrf-2. RESULTS: Our data showed higher liver enzymes in PCG compared with NCG. Additionally, we also found a significant decrease in Nrf-2, CAT, SOD, caspase 3, and caspase 9 levels and up-regulation of AKT and PI3K in the PCG relative to the negative control group. On the other hand, our findings suggest that Artichoke extract holds protective and therapeutic potential for effectively treating HCC induced by CCl4, especially in the APG. DISCUSSION: Our findings imply that the impressive antioxidant, apoptotic, and anticancer capabilities of Artichoke extract are due to the combination of the phenolic acids and flavonoids. Consequently, it is advisable to incorporate artichoke as a dietary supplement for individuals with chronic liver conditions. CONCLUSION: We conclude that the up-regulation of the Caspase 3 and Caspase 9 pathways and the suppression of PI3K/AKT signalling pathways may be the mechanisms behind the anti-tumor actions of artichoke extract.
Drug Release, Entrapment Efficacy, and Drug Loading Capacity of Taxanes Loaded Solid Lipid Nanoparticles (SLNs).
Valizadeh H, Mirzaei G, Arjmand A … +5 more , Nikkhah E, Seyyednia E, Khaleseh F, Ahmadi S, Saadat M
Anticancer Agents Med Chem · 2026 · PMID 41508960 · Publisher ↗
BACKGROUND: Solid lipid nanoparticles (SLNs) are submicron carriers with great promise in revolutionizing cancer therapy. They offer a potential solution to the side effects of conventional anticancer drugs, such as syst...
BACKGROUND: Solid lipid nanoparticles (SLNs) are submicron carriers with great promise in revolutionizing cancer therapy. They offer a potential solution to the side effects of conventional anticancer drugs, such as systemic toxicity and non-specific distribution. Taxanes, a widely used class of anticancer agents, have been increasingly incorporated into nano-lipid formulations (NLFs) to enhance their therapeutic index. OBJECTIVE: Designing optimal SLN formulations with enhanced drug loading capacity (DLC%), entrapment efficiency (EE%), and controlled drug release profiles is a significant challenge in pharmaceutical nanotechnology. This review, the first of its kind, systematically explores the key factors influencing EE%, DLC%, and the release behavior of Taxane-loaded SLNs. It provides a comprehensive and updated perspective, equipping you with the latest knowledge in this field. METHODS: This narrative review adopts a comprehensive approach to examine the formulation variables that affect EE%, including lipid type, drug properties, surfactants, co-surfactants, emulsifiers, and conjugates. It also outlines the critical parameters that influence drug release, such as particle size, co-loaded drugs, types of lipids and emulsifiers, surface modifiers, release media, and environmental conditions, including pH. The review process involved thoroughly analyzing existing literature and studies in pharmaceutical nanotechnology. RESULTS: Numerous studies demonstrate that EE% is significantly affected by the physicochemical properties of both the drug and lipid matrix and the choice and concentration of surfactants (e.g., Poloxamer, Tween-80, Solutol HS-15, lecithin). Certain modifications, such as conjugation with Hyaluronic acid, Chitosan derivatives, and PEGylation, tend to lower EE% but improve targeted release. Incorporation of compounds like α-lipoic acid, Ketoconazole, or co-loaded PTX and DTX results in a slower drug release profile. Conversely, siRNA incorporation often accelerates drug release. The release rate is also modulated by environmental pH and the nature of the lipid carriers. Ideal SLN formulations demonstrate high EE% and DLC% along with sustained and controlled release of Taxanes. CONCLUSION: Multiple formulation and environmental factors influence EE%, DLC%, and the drug release behavior of Taxane-loaded SLNs. Understanding these variables is not just important, but it is the key to rationalizing effective and stable nano-lipid formulations in cancer therapy. It is a fascinating and crucial area of study that demands our attention.
The Multi-pathway Mechanism and Co-delivery System of Oleanolic Acid Derivatives in Reversing Chemotherapy Resistance in Breast Cancer.
Yang K, Li Y, Zou Y … +6 more , Long W, Chen J, Dai M, Hong R, Feng W, Qian R
Anticancer Agents Med Chem · 2026 Jan · PMID 41503911 · Publisher ↗
Breast cancer threatens the health of women worldwide. However, the use of chemotherapy for breast cancer is prone to generating side effects and drug resistance. Therefore, identifying natural compounds with anticancer...
Breast cancer threatens the health of women worldwide. However, the use of chemotherapy for breast cancer is prone to generating side effects and drug resistance. Therefore, identifying natural compounds with anticancer activity is a better solution to the problem of drug resistance. Oleanolic acid (OA), a kind of pentacyclic triterpenoid, is widely studied and used in the field of oncology. It has biological activity against breast cancer and has few side effects on normal cells. OA can be used as a frame for chemical modification to synthesize new compounds for the development of new drugs. At present, some OA derivatives with anti-breast cancer biological activity have been proven clinically, while others have emerged as candidates. This review aims to provide a comprehensive understanding of the mechanisms of oleanolic acid and its derivatives on breast cancer from previous studies.
CD24 and Mutant p53: Emerging Therapeutic Targets in Prostate Cancer Progression.
Qinzhamusu Y, Xintian L, Zhihao G … +5 more , Tiezheng H, Ming Z, Ruishi X, Yi G, Yong W
Anticancer Agents Med Chem · 2026 · PMID 41503910 · Publisher ↗
INTRODUCTION: Prostate cancer is a leading cause of cancer-related mortality in men worldwide, and the treatment of metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge. CD24, a glyc...
INTRODUCTION: Prostate cancer is a leading cause of cancer-related mortality in men worldwide, and the treatment of metastatic castration-resistant prostate cancer (mCRPC) remains a major clinical challenge. CD24, a glycosylated cell surface protein, plays a critical role in tumor progression and immune evasion. This review focuses on the role of CD24 in prostate cancer pathogenesis, particularly its interaction with mutant p53, and explores potential therapeutic implications. METHODS: Through a systematic search of the PubMed, Web of Science, and Embase databases (2015-2025), using the following structured search terms: (CD24 OR "CD24 antigen") AND ("prostate cancer" OR "prostatic neoplasms") AND ("mutant p53" OR "TP53 mutation") AND ("targeted therapy" OR immunotherapy), relevant studies were identified and screened according to PRISMA guidelines. RESULTS: CD24 overexpression was significantly associated with high Gleason scores, metastasis, and poor prognosis. Mechanistically, CD24 promotes tumor progression by destabilizing p53 through the disruption of ARF-NPM interactions and by synergizing with mutant p53. Preclinical studies indicate that therapies targeting CD24, such as CAR-T cells and nanoparticle-based drug delivery systems, demonstrate potent anti-tumor effects. DISCUSSION: The CD24-p53 axis is amplified in mCRPC and interacts with androgen receptor signaling, while tumor microenvironment factors further enhance treatment resistance. CONCLUSION: CD24 and mutant p53 represent promising therapeutic targets in metastatic castration-resistant prostate cancer (mCRPC). Translating these targeting strategies into clinical practice may help overcome current therapeutic challenges and improve patient outcomes.
A Systematic Review of the Mechanistic Effects of Ginsenosides on Enhancing Radiotherapy and Providing Radioprotection.
Abdi S, Heidari-Soureshjani S, Rostamian S … +1 more , Raeisi E
Anticancer Agents Med Chem · 2026 · PMID 41487004 · Publisher ↗
INTRODUCTION/OBJECTIVE: Radiotherapy (RT) is a standard cancer treatment that may be associated with problems such as ineffectiveness and side effects. This study investigated ginsenosides' radiosensitizing and radioprot...
INTRODUCTION/OBJECTIVE: Radiotherapy (RT) is a standard cancer treatment that may be associated with problems such as ineffectiveness and side effects. This study investigated ginsenosides' radiosensitizing and radioprotective properties and their metabolites during RT. METHODS: This study searched databases including PubMed/MEDLINE, Scopus, Embase, and Cochrane Library for articles before January 28, 2025. After specifying the inclusion and exclusion criteria, relevant articles were imported into EndNote software and screened. Then, the data were recorded in tables and analyzed. RESULTS: After the screening process, 28 articles were included. Ginsenosides exhibited radioprotective effects in normal tissues by reducing oxidative stress, preserving mitochondrial integrity, enhancing DNA repair, modulating inflammatory pathways, and supporting hematopoiesis. Key compounds such as Rg1, Rg3, and Rh2 promoted tissue regeneration and protected against radiation-induced organ damage. In tumour cells, ginsenosides enhance radiosensitivity by increasing reactive oxygen species (ROS), disrupting mitochondrial function, inducing DNA damage and cell cycle arrest, and promoting apoptosis. They also inhibited tumour progression via nuclear factor kappa B (NF-κB) suppression and immune activation, reducing angiogenesis and metastasis. These dual actions suggest their potential to improve radiotherapy outcomes. DISCUSSION: Ginsenosides revealed dual roles as radioprotective and radiosensitizing agents, highlighting their potential in improving RT outcomes. However, the limited clinical data and lack of ginseng extract studies indicate the need for future clinical studies to establish optimal dosing, safety, and relevance for humans. CONCLUSION: The findings of both and studies indicated that ginsenosides enhance RT and provide protective effects against the harmful impacts of ionizing radiation.
FN-1501 Synergistically Enhances Almonertinib Efficacy in EGFR-TKI-Resistant Lung Adenocarcinoma through Ferroptosis Induction.
Feng S, Peng C, Zou D … +5 more , Wen S, Hu B, Zhu S, Du Y, Shen B
Anticancer Agents Med Chem · 2025 Nov · PMID 41293947 · Publisher ↗
INTRODUCTION: The emergence of acquired resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) presents a significant barrier to effective treatment in lung adenocarcinoma. This study inves...
INTRODUCTION: The emergence of acquired resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) presents a significant barrier to effective treatment in lung adenocarcinoma. This study investigates the antitumor efficacy of FN-1501 and its potential synergistic interaction with Almonertinib (Alm) to combat this resistance. METHODS: The impact of FN-1501 on lung adenocarcinoma and its synergistic effects with Almonertinib (Alm) were assessed through flow cytometry, Western blot analysis, CCK-8 assays, and clonogenic formation assays. Additionally, transcriptome analysis and network pharmacology were employed to elucidate the functional mechanisms by which FN-1501 may reverse EGFR-TKI acquired resistance. RESULTS: FN-1501 demonstrated the ability to inhibit cell proliferation, induce apoptosis, and arrest the cell cycle. The combination of Alm and FN-1501 restored sensitivity in resistant cell lines. Mechanistic investigations indicated that this combination triggered ferroptosis via the FOXO1-mediated upregulation of NCOA4. In vivo experiments showed that the Alm+FN-1501 combination significantly inhibited tumor growth compared to either treatment alone. DISCUSSION: These results provide compelling evidence that targeting ferroptosis pathways could be a viable approach to overcoming resistance to EGFR-TKIs. The FOXO1/NCOA4 axis emerges as a critical component in this process, enhancing our understanding of the mechanisms underlying resistance. While these findings are promising, further research is needed to evaluate toxicity, pharmacokinetics, and the applicability of this strategy in a broader context of resistance. Identifying predictive biomarkers could help refine patient selection for this treatment approach. CONCLUSION: FN-1501 exhibits significant antitumor activity and, when combined with Alm, effectively reverses EGFR-TKI resistance by inducing ferroptosis, highlighting its potential for clinical application.
Discovery of Lead Compounds Targeting Transcriptional Regulation.
Chen Y
Anticancer Agents Med Chem · 2026 · PMID 41208060 · Publisher ↗
Abstract loading — click title to view on PubMed.
ALG3 as a PanCancer Oncogene: Bioinformatics Analysis and Identification of Small-Molecule Inhibitors.
Hassan HM, Abdulsahib WK, Otifi HM … +9 more , Alshehri MA, Andarawi MO, Darwish KM, Elhady SS, Alshaya DS, Katouah HA, Althobaiti A, Fayad E, Eldeen MA
Anticancer Agents Med Chem · 2025 Nov · PMID 41185511 · Publisher ↗
INTRODUCTION: Glycosylation plays a crucial role in cellular processes such as recognition and signaling, and its dysregulation is associated with tumor progression. Alpha-1,3-mannosyltransferase (ALG3) is a key enzyme i...
INTRODUCTION: Glycosylation plays a crucial role in cellular processes such as recognition and signaling, and its dysregulation is associated with tumor progression. Alpha-1,3-mannosyltransferase (ALG3) is a key enzyme in N-glycosylation, and its aberrant expression has been implicated in various malignancies. However, the mechanisms underlying ALG3-driven oncogenesis and the identification of potential ALG3 inhibitors remain largely unexplored. This study aims to comprehensively investigate the oncogenic role of ALG3 across different cancer types and identify potential inhibitors through bioinformatics analysis and molecular dockingcoupled dynamics simulations. METHODS: Multiple cancer-related databases were analyzed to elucidate the oncogenic role of ALG and to assess its expression patterns, genetic alterations, and epigenetic regulation. Furthermore, molecular docking and dynamics simulations were employed to identify small-molecule inhibitors targeting the human ALG3. RESULTS: Our findings demonstrated a significant upregulation of ALG3 at both transcript and protein levels in cancerous tissues compared to normal ones. High ALG3 expression correlated positively with tumor stage, grade, and metastasis while negatively influencing patient survival. Genetic analysis revealed that amplification was the most common alteration in ALG3, whereas DNA methylation played a key role in its upregulation. Molecular docking and dynamics simulation identified two mannosyltransferase inhibitors, Opn and Clo, as potential inhibitors of ALG3, suggesting their therapeutic potential. DISCUSSION: This study highlights the oncogenic role of ALG3 in a pan-cancer model and identifies its potential inhibitors. Our findings provide valuable insights into ALG3-driven tumorigenesis and suggest that targeting ALG3 could be a promising strategy for cancer therapy. CONCLUSION: The study first reported potential inhibitors of human ALG3 based on a molecular modelling approach. This opens the way for future experimental investigations of the testing of these lead compounds in ALG3-high cancer models.
Metformin Inhibits the Growth of Hypopharyngeal Squamous Cell Carcinoma of Fadu Cell and Down-Regulates LncAROD to Improve Prognosis.
Liu F, Xie H, Liu M … +1 more , Wang D
Anticancer Agents Med Chem · 2025 Oct · PMID 41177792 · Publisher ↗
BACKGROUND: Hypopharyngeal Squamous Cell Carcinoma(HSCC) is associated with a poor prognosis due to challenges in early detection, early metastasis, and limited treatment options. OBJECTIVE: This study aims to investigat...
BACKGROUND: Hypopharyngeal Squamous Cell Carcinoma(HSCC) is associated with a poor prognosis due to challenges in early detection, early metastasis, and limited treatment options. OBJECTIVE: This study aims to investigate the effect of metformin on HSCC and identify potential prognostic factors associated with this carcinoma. METHODS: The effects of metformin in HSCC cells were tested by functional assays in vitro. A xenograft tumor model was established, which was further examined by H&E staining, immunohistochemistry, and transmission electron microscopy (TEM). RNA sequencing analysis was employed to investigate the effects of metformin on gene expression and associated pathways. Bioinformatic analysis was further conducted to elucidate potential mechanisms and their correlation with gene expression, the tumor immune microenvironment, and survival prognosis. Finally, we further assessed the effect on FaDu cells by knocking down lncAROD using siRNAs. RESULTS: The results demonstrated that metformin significantly reduced cell viability and migration, while promoting apoptosis and inducing cell cycle arrest in FaDu cells. WB analysis revealed that metformin inhibits the development of FaDu cells, possibly through the EMT pathway. In vivo studies indicate that metformin effectively inhibits tumor growth, promotes apoptosis, and autophagy. RNA-seq analysis revealed that metformin led to the upregulation of 1,697 genes and the downregulation of 858 genes, particularly highlighting a significant reduction in lncAROD, which were subsequently verified by qRT-PCR. Bioinformatic analysis demonstrated that lncAROD is highly expressed, with patients exhibiting higher levels of lncAROD showing poorer prognoses. Knockdown of lncAROD can reduce the proliferation, migration, and invasion of FaDu cells. CONCLUSION: This finding presents a novel approach to the clinical management of HSCC, indicating that metformin influences various processes related to the growth and progression of HSCC. Specifically, it reduces lncAROD expression and inhibits tumor progression, suggesting that lncAROD may serve as a valuable biomarker for evaluating the prognosis of HSCC.
Berberine Hydrochloride Inhibits the Proliferation and Tumorigenesis of Hepatocellular Carcinoma Cells by Regulating Amino Acid Metabolism.
Jian Q, Shu Y, Li Z … +5 more , Chi Q, Nisar MF, Wang C, Wang G, Xu K
Anticancer Agents Med Chem · 2025 Oct · PMID 41140218 · Publisher ↗
BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent cancer in the world and a highly fatal primary liver cancer. Berberine hydrochloride (BBH) has exhibited therapeutic potential against HCC with no toxicity and goo...
BACKGROUND: Hepatocellular carcinoma (HCC) is a frequent cancer in the world and a highly fatal primary liver cancer. Berberine hydrochloride (BBH) has exhibited therapeutic potential against HCC with no toxicity and good anti-tumor effects. OBJECTIVE: The objective of this study is to investigate the role of BBH against HCC and elucidate its underlying mechanism. METHODS: In Hep3B and HCCLM3 cell lines, the anti-tumor effects of BBH were assessed using MTT, wound healing, and colony formation assays, which measure cell viability, migration, and proliferation, respectively. Protein expression linked to apoptosis and cell cycle regulation was examined using western blotting. RNA sequencing and metabolomics analysis were performed to identify the metabolic and molecular targets of BBH, which were further confirmed by molecular docking. Furthermore, a tumor model was established by subcutaneous injection of Hep3B cells into nude mice to determine whether BBH has antitumor effects in vivo. RESULTS: Following adose-dependent manner, BBH efficiently reduced the viability, and enhanced migration, inducing cell cycle arrest via downregulation of CDK1 and CCND1. It also induced apoptosis by downregulating BCL2 and upregulating BAX. RNA-seq analysis revealed that BBH-treated cells had differentially expressed genes enriched in amino acid metabolic pathways. Furthermore, metabolomics analysis depicted BBH-mediated inhibition of alanine, methionine, and glutamic acid biosynthesis in HCC cells. Protein-protein interaction (PPI) network analysis and molecular docking studies have identified DOT1L, SMYD2, and KMT2C as potential molecular targets for BBH. Tumor samples were stained with HE and KI67 immunohistochemistry, and BBH significantly inhibited tumor growth in vivo. CONCLUSION: BBH may inhibit HCC tumorigenesis by disrupting amino acid metabolism and holds potential as a therapeutic agent for HCC.
Camel Milk in Skin Cancer Therapeutics: An In-vitro and In-vivo Study.
Jain N, Bagoria L, Keelka S … +5 more , Jain P, Khandelwal R, Sharma AK, Sharma MK, Kaushik P
Anticancer Agents Med Chem · 2025 Oct · PMID 41121517 · Publisher ↗
INTRODUCTION: Therapeutic applications of camel milk in various human ailments have led to the investigation of camel milk against multiple cancers. However, the absence of its scientific evidence in skin cancer protecti...
INTRODUCTION: Therapeutic applications of camel milk in various human ailments have led to the investigation of camel milk against multiple cancers. However, the absence of its scientific evidence in skin cancer protection has prompted this new study's inception. METHODS: The study includes estimation of camel milk's chemopreventive potential on A431 cells and a twostage skin carcinogenesis model (Mus musculus). The in-vitro studies included MTT, scratch and flow cytometry assay to determine the anti-proliferative effects, anti-migratory ability and cell numbers in various cell cycle stages. In the in-vivo study, estimations of tumour morphology, biochemical alterations, along with a histopathological study were performed. Further, the milk was assessed for its anti-oxidative activities, followed by GCMS analysis for the investigation of potential compounds. RESULTS: The in-vitro results demonstrated camel milk's dose-dependent anti-proliferation, significant (p<0.001) cell migration inhibition, and conclusive G1/S phase cell cycle arrest. The in-vivo study revealed a notable reduction in tumour parameters and histopathological lesions in skin and liver tissues of camel milk-treated mice. Additionally, a marked decrease (p<0.005; 0.001) in LPO levels and an increase in GSH, catalase and SOD biochemical parameters were noted. Moreover, dose-dependent elevation (p<0.001) of milk's anti-oxidative activity (DPPH, ABTS, ferrous-ion & superoxide-anion chelating) and presence of numerous anti-oxidative and anticancer compounds was observed. DISCUSSIONS: The investigation highlightstranslational relevance of camel milk's in-vitro outcomes as supported by in-vivo findings. Moreover, GC-MS analysis and anti-oxidative potential underscore the mechanism behind the observed chemo-prevention. CONCLUSIONS: The study reveals camel milk's significant chemo-preventive efficacy primarily due to its robust antioxidant properties, making it a promising adjunct skin cancer therapy.
Jianpi Yiwei Granules for Chemotherapy-Induced Gastrointestinal Reactions: A Randomized Double-Blind Placebo-Controlled Trial.
Cai K, Chen J, Li N … +1 more , Feng L
Anticancer Agents Med Chem · 2026 · PMID 41114481 · Publisher ↗
INTRODUCTION: Chemotherapy-induced gastrointestinal reactions are common in non-small cell lung cancer (NSCLC) patients undergoing carboplatin-based chemotherapy. Jianpi Yiwei granules (JPYW), a traditional Chinese medic...
INTRODUCTION: Chemotherapy-induced gastrointestinal reactions are common in non-small cell lung cancer (NSCLC) patients undergoing carboplatin-based chemotherapy. Jianpi Yiwei granules (JPYW), a traditional Chinese medicine (TCM) formula, can alleviate these symptoms. MATERIALS AND METHODS: This multi-center, randomized, double-blind, placebo-controlled trial enrolled 136 NSCLC patients scheduled for carboplatin-based chemotherapy. Participants were randomly assigned to the treatment group (JPYW with standard antiemetic drugs) and the control group (placebo with standard antiemetic drugs). The complete control rate of nausea and vomiting was assessed using the Visual Analog Scale (VAS) and patient diaries. Control of anorexia, bloating, constipation, and quality of life was measured using the Functional Living Index-Emesis scale and the Brief Fatigue Inventory (BFI). RESULTS: The primary objective of this study was to assess the efficacy of JPYW in alleviating non-vomiting digestive symptoms, such as nausea and anorexia, in NSCLC patients receiving carboplatin-based chemotherapy. The secondary objective was to evaluate its effect on improving bloating, constipation, quality of life, and safety. DISCUSSION: Previous studies have shown that Chinese herbs, such as ginger, are effective in treating chemotherapy- induced nausea and vomiting (CINV). JPYW, a multi-component TCM formula, contains active compounds from and . JPYW exerts anti-inflammatory and prokinetic effects that can synergistically regulate gastrointestinal functions. Preliminary observations confirmed the safety of JPYW combined with standard chemotherapy. CONCLUSION: The current findings contribute to the treatment of adverse reactions to tumor chemotherapy and are expected to improve the quality of life for chemotherapy patients.
The EP300-Targeting Drug CCS1477 Inhibits the Growth and Development of Diffuse Large B-Cell Lymphoma by Promoting Apoptosis and Mitophagy to Reduce Drug Resistance.
Si R, Zhang Y, Hu B … +13 more , Du Y, Zou D, Wen S, Du X, Peng C, Chen X, Fu S, Zhu S, Du F, Sha X, Ding N, Xu C, Shen B
Anticancer Agents Med Chem · 2025 Oct · PMID 41088985 · Publisher ↗
INTRODUCTION: Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) develop primary resistance or relapse, owing to the high heterogeneity and aggressive nature of the disease. Consequently, novel drug...
INTRODUCTION: Approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) develop primary resistance or relapse, owing to the high heterogeneity and aggressive nature of the disease. Consequently, novel drugs are urgently needed to improve outcomes in patients who are resistant. METHODS: This study quantified the anti-proliferative effects of CCS1477 in vitro using the Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, and lactate dehydrogenase measurement. Flow cytometry and Western blot analyses were performed concurrently to investigate the induction of apoptosis and the activation of mitophagy. The efficacy and safety of CCS1477 were evaluated in in vivo models. To elucidate the mechanism, cell lines with EP300 knockdown and overexpression were established. Functional assays and Western blot analyses revealed that EP300 regulates apoptosis, mitophagy, and c-MYC-mediated drug-resistant phenotypes. RESULTS: This study demonstrated that CCS1477, a highly selective EP300/CBP bromodomain inhibitor, significantly suppressed the progression of diffuse large B-cell lymphoma. The study revealed that CCS1477 dosedependently inhibited the proliferation of diffuse large B-cell lymphoma cells and induced apoptosis and mitophagy. Mechanistically, EP300 downregulation promoted apoptosis and activated the PINK1-dependent mitophagy pathway while suppressing c-MYC-mediated drug resistance genes, ultimately inhibiting DLBCL cell proliferation. In animal models, CCS1477 significantly reduced tumor volume and extended doubling time, providing the first evidence of its in vivo antitumor activity against DLBCL. DISCUSSION: Through systematic in vitro and in vivo investigations, this study validated the significant therapeutic promise of EP300/CBP inhibitor CCS1477 for diffuse large B-cell lymphoma. However, the mechanistic basis for differential sensitivity across DLBCL subtypes, along with long-term efficacy and potential adverse effects, requires comprehensive investigation. Notably, EP300 has been verified as a novel prognostic biomarker and therapeutic target; this work establishes an innovative epigenetic-targeted strategy for relapsed/refractory diffuse large B-cell lymphoma. CONCLUSION: By selectively targeting EP300, CCS1477 orchestrates a dual pro-death mechanism involving both intrinsic apoptosis execution and PINK1-driven mitochondrial clearance, resulting in significant inhibition of diffuse large B-cell lymphoma pathogenesis.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe