Medicine in Drug Discovery最新文献

{"title":"The effects of patent term extension on new drug patent protection in China, Europe, and the United States","authors":"Hai-Long Zhang ,&nbsp;Yongxia Li","doi":"10.1016/j.medidd.2026.100252","DOIUrl":"10.1016/j.medidd.2026.100252","url":null,"abstract":"<div><div><strong>Background:</strong> China<!--> <!-->has recently introduced patent term buchang (PTB) for new drugs. This study presents a systematic profile for China’s PTB, European SPC, and the U.S. PTE for new drug protection. <strong>Methods:</strong> Drug Development Time Period (DDTP) index and Final Drug Patent Protection Term (FDPPT) were calculated using predefined equations. <strong>Results:</strong> Our study showed the average PTB, SPC, and PTE for new drugs were 3.56, 4.11, and 2.82 years, respectively. Consequently, the average FDPPT<!--> <!-->for these regions reached 11.20, 14.32, and 13.19 years,<!--> <!-->respectively. Our results revealed that the average DDTP index for these new drugs was 9.79 years in Europe, 12.36 years in China, and 10.05 years in the US. For the same drugs, the SPC term in Europe was 1.55 years longer than the PTE in the United States. The FDPPT in Europe was an average of 0.54 years longer than that in the US. <strong>Conclusions:</strong> Our study<!--> <!-->characterizes<!--> <!-->China’s PTB<!--> <!-->profile for the first time<!--> <!-->and proposes a novel methodology-the DDTP index concept and its quartile range method-for investigating patent extension protection. The study shows that for new drugs with a DDTP index between 6 and 10 years, patent protection in Europe is substantially longer than in China and the US. For those drugs with an index between 10 and 15 years, Europe still offers the longest protection period (Avg. 13.41 years), while China has the shortest (Avg. 11.86 years); the US falls in the middle (Avg. 12.83 years). However, for drugs with a DDTP index above 10 years, the relative advantage of patent term extension in Europe diminishes and eventually disappears as the index increases.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"30 ","pages":"Article 100252"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of mitragynine levels with lipid profiles in regular kratom (Mitragyna speciosa) users","authors":"Slamet Wahyono ,&nbsp;Mery Budiarti ,&nbsp;Lusi Kristiana ,&nbsp;Aris Yulianto ,&nbsp;Weny Lestari ,&nbsp;Rohmat Mujahid ,&nbsp;Agung Eru Wibowo ,&nbsp;Lola Ayu Istifiani ,&nbsp;Zulvikar Syambani Ulhaq","doi":"10.1016/j.medidd.2025.100241","DOIUrl":"10.1016/j.medidd.2025.100241","url":null,"abstract":"<div><div>Kratom (<em>Mitragyna speciosa</em>) is widely consumed in Southeast Asia for both medicinal and recreational purposes, yet its impact on human health remains unclear. This study examined sociodemographic factors, consumption patterns, serum mitragynine (MG) levels, and clinical chemistry parameters among 90 male participants from the Putussibau District, West Kalimantan, Indonesia. Participants were categorized into kratom users (n = 64) and non-users (n = 26). The majority of users indicated that they consumed kratom for health-related reasons, most commonly for 2–5 years, and nearly half reported daily intake exceeding 21 leaves. Serum MG concentrations were significantly higher among users than non-users, although no associations were observed with duration or intensity of consumption. Clinical chemistry analysis revealed that kratom users had lower levels of LDL, BUN, urea, and creatinine, alongside higher eGFR values, while no significant differences were detected in liver enzymes, glucose, HDL, triglycerides, or inflammatory markers. Notably, serum MG was negatively correlated with LDL and triglyceride levels. Stratified analysis indicated that long-term use was associated with favorable hepatic and lipid profiles, suggesting possible adaptive metabolic responses, whereas higher daily intake produced mild, subclinical elevations in liver and renal markers. Additionally, systemic inflammation, reflected by increased hsCRP and IL-6, was linked to self-reported anxiety, highlighting a potential peripheral mechanism connecting kratom use to central nervous system (CNS) effects. Overall, these findings suggest that regular kratom use may elicit adaptive physiological changes with minimal biochemical perturbation at moderate intake levels. Further longitudinal and mechanistic studies are warranted to clarify causal pathways and long-term health implications of kratom use.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100241"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From ferments to fixers: Postbiotics in wound healing","authors":"Hui Sin Lim ,&nbsp;Christopher J. Serpell ,&nbsp;Satoshi Ogawa ,&nbsp;Yong Yu Hu ,&nbsp;Eng Hwa Wong","doi":"10.1016/j.medidd.2026.100249","DOIUrl":"10.1016/j.medidd.2026.100249","url":null,"abstract":"<div><div>The skin acts as a vital barrier against the environment, and injuries can lead to acute or chronic wounds. Chronic wounds often heal slowly and are more susceptible to infection. Postbiotics, defined as preparations of inactivated microorganisms or their bioactive components, have demonstrated potential to promote wound repair. Compared with live probiotics, postbiotics are safer, more stable, and easier to standardise, while still supporting tissue repair via antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory effects. Compounds such as exopolysaccharides, short-chain fatty acids, antimicrobial peptides, enzymes, vitamins, and cell-free supernatants can enhance fibroblast growth, collagen production, keratinocyte migration, angiogenesis, and immune balance. Postbiotics derived from <em>Lactobacillus</em>, <em>Bifidobacterium</em>, <em>Bacillus</em>, and commensal <em>Staphylococcus</em> species act through multiple signalling pathways. They reduce pro-inflammatory cytokines, promote alternatively activated M2 macrophage polarisation, and facilitate restoration of the skin barrier. Recent developments in hydrogels, nanofibers, and encapsulated delivery systems have improved the stability and availability of postbiotic compounds at wound sites, making them more effective. Despite promising results from preclinical studies and early clinical trials, challenges remain in standardizing production, defining regulatory frameworks, and generating strong clinical evidence. Future studies should focus on identifying key bioactive molecules using advanced omics approaches, developing targeted delivery systems, and evaluating postbiotic therapies in well-designed clinical trials. Overall, postbiotics provide a safe and versatile approach to accelerate wound healing and may serve as an alternative or complement to conventional treatments.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100249"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward peptide-based protein replacement in fragile X syndrome: Evaluating the N-tat strategy","authors":"Oliver A. Kent","doi":"10.1016/j.medidd.2025.100244","DOIUrl":"10.1016/j.medidd.2025.100244","url":null,"abstract":"<div><div>Fragile X syndrome (FXS), a leading inherited cause of intellectual disability and autism, arises from loss of the RNA-binding protein FMRP and consequent dysregulation of synaptic mRNA translation. No clinically approved therapies exist to restore FMRP function. A recent study showed that a Tat-conjugated FMRP fragment spanning residues 1–297 (FMRP N-tat) can transiently reduce hyperexcitability in an FXS mouse model, supporting peptide replacement as a feasible therapeutic strategy. Extending this concept, Leguay et al. demonstrated in FXS patient iPSC-derived neurons that N-tat reconstitutes interactions with endogenous protein partners correcting dysregulated translation and mitochondrial defects. However, despite recapitulating several functions of full-length FMRP, the in vivo effects of N-tat remain short-lived, highlighting challenges in stability and the potential need for additional functional domains. Herein, this commentary outlines both the promise of N-tat–based protein replacement and the remaining gaps that must be addressed to achieve clinically durable restoration of FMRP function.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100244"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145840054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rapid at-line LC-QTOF-MS/MS based targeting and guided isolation approach uncovers 2-methoxy-1,4-naphthoquinone from Impatiens balsamina Linn. as an anti-Malassezia agent","authors":"Weerapong Juntachai ,&nbsp;Kantarawee Khayhan ,&nbsp;Piyakaset Suksathan ,&nbsp;Sathid Aimjongjun ,&nbsp;Supang Khondee ,&nbsp;Ruttanaporn Chantakul ,&nbsp;Nantaka Khorana ,&nbsp;Nitra Nuengchamnong ,&nbsp;Jukkarin Srivilai","doi":"10.1016/j.medidd.2026.100251","DOIUrl":"10.1016/j.medidd.2026.100251","url":null,"abstract":"<div><h3>Background</h3><div><em>Impatiens balsamina</em> Linn. is an annual plant traditionally used to treat several cutaneous fungal infections, including conditions often associated with <em>Malassezia</em> spp. However, its anti-<em>Malassezia</em> activity, biomarkers, and underlying mechanisms remain insufficiently defined. This study establishes a rapid at-line LC-ESI-QTOF-MS/MS screening platform coupled with a colorimetric antifungal assay to identify anti-<em>Malassezia</em> biomarkers and assess their modes of action.</div></div><div><h3>Methods</h3><div>An at-line LC-ESI-QTOF-MS/MS platform was used to screen <em>I. balsamina</em> extracts and identify bioactive constituents. The most active extract was subjected to preparative HPLC for isolation of biomarkers. The resazurin-based microdilution antifungal assays were performed against <em>M. furfur</em>. The mechanisms of action of the identified compounds were investigated by lipase assay and biofilm formation assay.</div></div><div><h3>Results</h3><div>The ethyl acetate extract exhibited the most potent antifungal activity. The LC-ESI-QTOF-MS/MS and bioactive chromatograms pinpointed 2-methoxy-1,4-naphthoquinone (2MN) as the only active compound. Purified 2MN showed MIC values of 6.510 ± 1.906 µg/mL and MFC values of 8.854 ± 4.543 µg/mL. The compound reduced extracellular lipase activity and effectively inhibited biofilm formation of <em>M. furfur</em>.</div></div><div><h3>Conclusions</h3><div>The at-line LC-ESI-QTOF-MS/MS platform successfully guided and reduced the time and sample scale for purification of the anti-<em>Malassezia</em> compound. 2MN from <em>I. balsamina</em> exerts a significant antifungal effect and reduces fungal biofilm. Our rapid targeting approach and findings here encourage the discovery of antifungal phytochemicals as a candidate for anti-<em>Malassezia</em> therapy.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100251"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of α-glucosidase by melatonin derivatives: insights from kinetics, docking, and molecular dynamics simulations","authors":"Ploenthip Puthongking ,&nbsp;Bodee Nutho ,&nbsp;Muhammad Subhan ,&nbsp;Juthamat Ratha ,&nbsp;Kiattawee Choowongkomon ,&nbsp;Saranyu Khammuang ,&nbsp;Kamonpan Sanachai","doi":"10.1016/j.medidd.2025.100240","DOIUrl":"10.1016/j.medidd.2025.100240","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) represents a major global health challenge, emphasizing the need for effective strategies to manage postprandial hyperglycemia. Inhibition of α-glucosidase, a key enzyme involved in carbohydrate digestion, is a well-established therapeutic approach. In this study, melatonin, an indoleamine with diverse biological activities, was investigated as a scaffold for the development of novel α-glucosidase inhibitors. Among the derivatives evaluated, 4EBM emerged as the most potent inhibitor, exhibiting an IC₅₀ value of 37.20 ± 0.64 μM and demonstrating greater potency than the standard drug, acarbose. Kinetic studies, molecular docking, and molecular dynamics (MD) simulations indicated that 4EBM acts as a competitive inhibitor by directly interacting with key residues (Y158, F178, Q279, R315, and R442) within the α-glucosidase active site. Furthermore, <em>in silico</em> predictions suggested that several derivatives containing naphthalene, biphenyl, or trifluoromethylphenyl moieties exhibited stronger binding affinities than 4EBM. These findings underscore the potential of melatonin derivatives as promising lead compounds for the development of more effective α-glucosidase inhibitors for T2DM management, while also enhancing the current understanding of indoleamine scaffolds in enzyme inhibition.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100240"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous and oral NOAEL doses of the new PrC-210 aminothiol in swine and dose equivalency in humans to enable clinical trials","authors":"William E. Fahl ,&nbsp;Bryan L. Fahl ,&nbsp;Aaron M. Dingle","doi":"10.1016/j.medidd.2026.100248","DOIUrl":"10.1016/j.medidd.2026.100248","url":null,"abstract":"<div><div>Reactive Oxygen Species (ROS)-induced cell and organ toxicity is a common element in human disease patho-mechanisms. PrC-210 is a new free-radical scavenger that substantially suppresses ROS damage in pre-clinical animal disease models. Here we determined PrC-210 pharmacokinetic and toxicokinetic performance in a large animal pig model as a forestep to Phase 1 safety studies in humans. Using a newly created LC-MS assay to measure plasma PrC-210 levels, we determined that: i) an IV or oral PrC-210 bolus dose yielded easily measurable plasma concentrations, which returned to baseline within an hour (IV) or 8–10 h (oral), ii) at the same IV mg/kg dose, female pig plasma PrC-210 AUC levels were 13–15 % higher than males; this presumably reflects less vasculature per unit tissue mass, iii) a primary toxicity, vomiting, followed simple PrC-210 plasma toxicokinetics for both IV and oral doses, and was absent at IV PrC-210 NOAEL (5.0 mg/kg bw) and oral PrC-210 NOAEL (70.0 mg/kg bw) doses that are at least two-fold higher than the highest PrC-210 dose that would be administered therapeutically, iv) no significant changes in blood cell populations were seen through 7 days following an IV PrC-210 bolus NOAEL dose, v) no significant changes in any of 15 blood chemistry parameters were seen through 7 days following an IV PrC-210 NOAEL dose, and vi) no discernible visible nor histologic organ or tissue pathology was seen in necropsies performed at 7 days post-IV dose. This study supports continued development of PrC-210 for Phase 1 human studies.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100248"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146037563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning based analysis of the risks of combination aspirin and rivaroxabane antithrombotic therapy with nonsteroid anti-inflammatory drugs after arthroplasty","authors":"Vladimir U. Emelianov ,&nbsp;Sergey A. Khripunov ,&nbsp;Evgeniya A. Mikishanina ,&nbsp;Nikolai S. Nikolaev","doi":"10.1016/j.medidd.2025.100243","DOIUrl":"10.1016/j.medidd.2025.100243","url":null,"abstract":"<div><h3>Objective</h3><div>Thromboprophylaxis is essential following major joint surgery. While aspirin is widely discussed as a postoperative prophylactic alternative to heparin or rivaroxaban, it is often co-administered with NSAIDs for pain relief. The safety of such combinations remains unclear. This study uses multivariate machine learning (ML) analysis to compare bleeding risks between aspirin and rivaroxaban, and between their respective combinations with ketorolac or celecoxib.</div></div><div><h3>Methods</h3><div>We conducted a retrospective study of 1164 patients who underwent primary total knee or joint arthroplasty. ML was applied to model the risk of bleeding based on the clinical factors.</div></div><div><h3>Results</h3><div>The analysis revealed a minimal difference in bleeding risk between aspirin (odds ratio [OR] = 1.042, 95 % confidence interval [CI] = 0.762–1.426, 1.000) and rivaroxaban (OR = 0.959, 95 % CI = 0.701–1.312, p = 1.000). Concomitant use of ketorolac with either anticoagulant non-significantly increased the risk of bleeding (OR = 1.077, 95 % CI = 0.787–1.473, p = 0.337), in contrast, the combination with celecoxib was associated with a reduced risk (OR = 0.751, 95 % CI = 0.549–1.028, p = 0.0008). Multivariable logistic regression demonstrated the highest predictive value (AUC = 0.68), along with the best F1 score and Matthews correlation coefficient (0.32 and 0.22, respectively).</div></div><div><h3>Conclusion</h3><div>Aspirin and rivaroxaban appear to be interchangeable with respect to bleeding risk. While combining these anticoagulants with ketorolac did not significantly affect bleeding risk, the combination with celecoxib was associated with a lower risk. Therefore celecoxib may be preferable NSAID for analgesia in this context.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100243"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145748015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-derived metabolites in cancer: Dual roles in pathogenesis and opportunities for therapy","authors":"Muskan Rajak ,&nbsp;Debabrata Dash ,&nbsp;Raj Kumar Koiri","doi":"10.1016/j.medidd.2025.100245","DOIUrl":"10.1016/j.medidd.2025.100245","url":null,"abstract":"<div><div>The gut microbiota has emerged as a determinant of onset, progression, and response to treatment of many cancers. The current research in oncology indicates that microbial metabolites like short-chain fatty acids (SCFAs), secondary bile acids, indole derivatives, and polyamines are not passive metabolic end products but potent bioactive mediators. These molecules directly modulate cellular signaling pathways, immune modulation, and the tumor microenvironment. Depending on their concentration and the overall physiological environment, these metabolites may be tumorigenic or protective, anticancer in effect. Significantly, by controlling immune reactions and drug metabolism, microbiota-derived metabolites have been reported to modulate and enhance the activity of chemotherapeutic agents, radiotherapy, and immunotherapeutic protocols.</div><div>In spite of these advances, it is still difficult to apply microbiome research to clinical oncology. Some of the key hurdles are high interindividual heterogeneity in gut microbial structure, lack of standardized analysis pipelines, and incomplete understanding of mechanistic crosstalk between the host and microbiome. This heterogeneity makes reproducibility tricky and reduces the predictive value of microbiota-directed interventions in oncology. However, emerging advances in metabolomics, synthetic biology, and systems-level medicine are enabling personalized therapy discovery. Such technological advances facilitate massive profiling and individually customized modulation of microbial metabolites, thus promoting the development of metabolite-directed or microbiota-targeted adjuvant strategies that promise augmented specificity and therapeutic efficacy.</div><div>This review integrates existing knowledge, translational hurdles, and new trends in the translation of microbiome-derived metabolites towards precision cancer treatment. As the evidence increasingly places the gut microbiota at the interface of controlling and predicting tumor behavior and outcomes of therapy, it is a promising system for therapeutic and biomarker development. Translating these microbial metabolites by combining biotechnological and computational approaches can usher in a new era for precision oncology that is reconcilable with host–microbiome physiologies.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100245"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the therapeutic potential of plumbagin in breast cancer via advanced nanomedicine approaches","authors":"K.Trideva Sastri ,&nbsp;N.P. Gana ,&nbsp;Nischal Chandra ,&nbsp;Rupshee Jain ,&nbsp;Vikas Jain","doi":"10.1016/j.medidd.2026.100250","DOIUrl":"10.1016/j.medidd.2026.100250","url":null,"abstract":"<div><div>Plumbagin, a bioactive naphthoquinone from Plumbago species, has emerged as a pleiotropic anticancer candidate with activity across major breast cancer subtypes. Preclinical evidence indicates that plumbagin suppresses tumour growth by converging on redox stress and survival circuitry, including mitochondrial apoptosis and NF-κB-linked pathways, with reported inhibitory effects in ER-positive, HER2-overexpressing, and triple-negative models and a signal of relative selectivity in normal breast cells. Beyond cytotoxicity, plumbagin can attenuate metastatic programs, notably by NF-κB-dependent repression of CXCR4, thereby reducing migration and invasion. However, its clinical plausibility is constrained by poor solubility, exposure instability, and a narrow therapeutic window driven by quinone-mediated off-target oxidative burden. Advanced nanocarriers offer a rational strategy to convert this redox liability into tumour-selective benefit through exposure shaping, stimulus-responsive release, and conservative, clinically familiar excipient choices. Emerging designs—including long-circulating systems, ROS/GSH-activated approaches, and antioxidant interface engineering—aim to flatten peak-related toxicity while sustaining intratumoural pharmacodynamic thresholds. Co-delivery platforms may further synchronize pharmacology to overcome resistance, pairing plumbagin with cytotoxins or pathway modulators through programmable release sequencing. Looking ahead, AI/ML-guided formulation and imaging-integrated theranostics can support biomarker-driven dose selection and a pragmatic Phase I roadmap that adheres to transparent CMC principles. Collectively, these advances position plumbagin-based nanomedicine as a credible, mechanism-informed phytotherapeutic strategy for breast cancers with high unmet need, warranting carefully designed translational studies.</div></div>","PeriodicalId":33528,"journal":{"name":"Medicine in Drug Discovery","volume":"29 ","pages":"Article 100250"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}