Biomolecules最新文献

{"title":"Overview of Proteomic Analysis of Amyloid Plaques and Neurofibrillary Tangles in Alzheimer's Disease.","authors":"Amber Grewal, Simran Raikundalia, Joseph Zaia, Manveen K Sethi","doi":"10.3390/biom15091310","DOIUrl":"10.3390/biom15091310","url":null,"abstract":"<p><p>In this review, we describe the methods used for the extraction and mass spectrometry proteomics analysis of amyloid plaques and neurofibrillary tangles (NFTs), the two primary pathological hallmarks of Alzheimer's disease (AD). We also provide a comprehensive overview of the mass spectrometry-based studies conducted to analyze these pathological features. AD is the most prevalent form of dementia and the sixth leading cause of death in the United States. While the current treatments can alleviate early-stage memory and cognitive symptoms, they do not offer a cure. Thus, there is a pressing need to deepen our understanding of the neuropathological mechanisms underlying AD and to develop more effective therapeutics. In-depth mass spectrometry-based proteomics analyses of AD pathology-specifically, extracellular the Aβ plaques found in extracellular spaces and blood vessel walls and intraneuronal NFTs composed of the microtubule-associated protein tau-may offer molecular-level observations that contribute to the understanding of the biological context of plaque and NFT formation and support the discovery of potential biomarkers and therapeutic targets for AD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Duplication, Translocation, and Molecular Evolution of <i>Dmrt1</i> and Related Sex-Determining Genes in Anurans.","authors":"Sagar S Shinde, Paris Veltsos, Wen-Juan Ma","doi":"10.3390/biom15091306","DOIUrl":"10.3390/biom15091306","url":null,"abstract":"<p><p>Sex determination, the developmental process that directs embryos toward male or female fates, is controlled by master sex-determining genes whose origins and evolutionary dynamics remain poorly understood outside of a few model systems. In contrast to the highly differentiated sex chromosomes of mammals, birds, and <i>Drosophila</i>, most anurans (frogs and toads) maintain homomorphic sex chromosomes that exhibit a rapid turnover, even among closely related species. Master sex-determining genes evolve via gene duplication or via allelic diversification, and sex chromosome turnover is driven by gene translocation or novel mutations in the existing genes involved in the sexual developmental pathway. To uncover the mechanisms underlying the emergence of master sex-determining genes and sex chromosome turnover, we analyzed 53 published anuran genomes and one caecilian genome (>200 Mya divergence) and available transcriptomes. We asked how often master sex-determining genes arise by gene duplication, whether and how often gene translocation associates with sex chromosome turnover, and if master sex-determining genes evolve under positive selection. We find that chromosome-level synteny is remarkably conserved, with only a few fusions or fissions and no evidence for translocation of four candidate master sex-determining genes (<i>Dmrt1</i>, <i>Foxl2</i>, <i>Bod1l</i>, and <i>Sox3</i>). Only <i>Dmrt1</i> duplicated in 3 out of 50 species (excluding tetraploid <i>Xenopus</i>), and it showed strong testis-biased expression in all 8 species with available gonadal expression data. While <i>Dmrt1</i> has evolved under purifying selection, <i>Dmrt1</i> duplicates exhibit elevated nonsynonymous substitution rates and tendency towards positive selection. Lineage-specific amino acid changes were observed in the conserved DM domain of <i>Dmrt1</i>. These results demonstrate that, in anurans, master sex-determining genes rarely arise via gene duplication, and more likely evolve via allelic diversification. Sex chromosome turnover is not associated with gene translocation and is more likely driven by mutations on genes involved in sexual developmental pathways. All candidate sex-determining genes were under strong purifying selection, with the exception of duplications which are linked to positive selection. Our results suggest future research on anuran sex determination and sex chromosome evolution should focus on identifying allelic diversification and novel mutations on genes involved in sexual developmental pathways.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isoniazid-Derived Hydrazones Featuring Piperazine/Piperidine Rings: Design, Synthesis, and Investigation of Antitubercular Activity.","authors":"Esma Özcan, Siva Krishna Vagolu, Rasoul Tamhaev, Christian Lherbet, Lionel Mourey, Tone Tønjum, Miyase Gözde Gündüz, Şengül Dilem Doğan","doi":"10.3390/biom15091305","DOIUrl":"10.3390/biom15091305","url":null,"abstract":"<p><p>Isoniazid (isonicotinic acid hydrazide, INH) is a key drug used to treat tuberculosis (TB), which continues to be the world's most lethal infectious disease. Nevertheless, the efficacy of INH has diminished because of the emergence of <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) strains that are resistant to INH. Our goal in this study was to modify INH to reduce this significant resistance chemically. We synthesized INH-based hydrazones (<b>IP1</b>-<b>IP13</b>) through the reaction of INH with in-house obtained benzaldehydes carrying a piperidine or piperazine ring in refluxing ethanol. Upon confirmation of their proposed structures by various spectral techniques, <b>IP1</b>-<b>IP13</b> were evaluated for their antimycobacterial capacity against <i>Mtb</i> H37Rv strain and INH-resistant clinical isolates with <i>katG</i> and <i>inhA</i> mutations using the Microplate Alamar Blue Assay (MABA). The compounds were additionally tested for their cytotoxicity. The obtained data indicated that the compounds with moderately increased lipophilicity compared to INH (<b>IP7</b>-<b>IP13</b>) were promising antitubercular drug candidates, exhibiting drug-like properties and negligible cytotoxicity. Out of these, <b>IP11</b> (<i>N</i>'-(4-(4-cyclohexylpiperazin-1-yl)benzylidene)isonicotinohydrazide) emerged as the most promising derivative, demonstrating the lowest MIC values against all <i>Mtb</i> strains tested. Subsequently, the target molecules were evaluated for their capacity to inhibit enoyl acyl carrier protein reductase (InhA), the main target enzyme of INH. Except for <b>IP11</b> demonstrating 81% InhA inhibition at a concentration of 50 μM, direct InhA inhibition was shown not to be the primary mechanism responsible for the antitubercular activity of the compounds. The binding mechanism of <b>IP11</b> to InhA was analyzed through molecular docking and molecular dynamics simulations. Altogether, our research identified a novel approach to modify INH to address the challenges posed by the rising prevalence of drug-resistant <i>Mtb</i> strains.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Compounds as Modulators of Ferroptosis: Mechanistic Insights and Therapeutic Prospects in Breast Cancer.","authors":"Haotong He, Haoyang Yu, Hefeng Zhou, Guozhen Cui, Min Shao","doi":"10.3390/biom15091308","DOIUrl":"10.3390/biom15091308","url":null,"abstract":"<p><p>Breast cancer is the most prevalent malignant tumor in women. However, its clinical management is severely hindered by three interconnected challenges that limit long-term survival: treatment resistance, metastatic dissemination, and immunological evasion. Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a novel strategy to overcome these obstacles. Furthermore, it demonstrates significant potential in inhibiting tumor metastasis and modifying the anti-tumor immune microenvironment, which provides a novel approach to address the core dilemma of breast cancer. Natural products have emerged as significant sources of ferroptosis inducers owing to their distinctive chemical variety, multi-target regulatory capabilities, and acceptable safety profile. Data increasingly indicates that several natural compounds can function as effective inducers or sensitizers of ferroptosis cell death. This review provides a thorough evaluation of current progress in harnessing natural ingredients to trigger ferroptosis for breast cancer treatment. It also elucidates the fundamental molecular mechanisms. Furthermore, it encapsulates therapeutic efficacy in preclinical models. Ultimately, it rigorously evaluates existing constraints and delineates potential and barriers for clinical translation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Product-Derived Drugs: Structural Insights into Their Biological Mechanisms.","authors":"Yujeong Choi, Younghyun Kim, Hye Joon Boo, Danbi Yoon, Jeong Seok Cha, Jiho Yoo","doi":"10.3390/biom15091303","DOIUrl":"10.3390/biom15091303","url":null,"abstract":"<p><p>Natural product-derived drugs represent a cornerstone of modern pharmacotherapy, with many serving as essential therapeutic agents across diverse medical conditions. Recent advances in structural biology have provided unprecedented insights into the molecular mechanisms underlying their biological activities. This review presents a comprehensive structural analysis of five representative natural product-derived drugs: digoxin, simvastatin, morphine, paclitaxel, and penicillin. Through an examination of high-resolution crystal structures and cryo-electron microscopy (cryo-EM) data, we elucidate how these compounds interact with their respective protein targets and modulate biological functions. The structural data reveal diverse binding mechanisms-ranging from competitive inhibition and covalent modification to allosteric modulation via conformational selection and induced fit-demonstrating how natural products achieve their therapeutic effects through precise molecular recognition. These structural insights provide a molecular foundation for understanding natural product pharmacology and offer valuable guidance for structure-based drug design approaches in developing next-generation therapeutics.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrospinal Fluid Erythrocyte Burden Amplifies the Impact of PTAU on Entorhinal Degeneration in Alzheimer's Disease.","authors":"Rafail C Christodoulou, Georgios Vamvouras, Vasileia Petrou, Platon S Papageorgiou, Rafael Pitsillos, Ludwing Rivera, Evros Vassiliou, Sokratis G Papageorgiou, Elena E Solomou, For The Alzheimer's Disease Neuroimaging Initiative","doi":"10.3390/biom15091300","DOIUrl":"10.3390/biom15091300","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) involves ongoing neurodegeneration, with phosphorylated tau (PTAU) intracellular accumulation closely associated with cortical shrinking. However, not everyone with high PTAU levels shows the same degree of neurodegeneration, implying that other biological stress factors might influence tau's harmful effects. This research explores whether cerebrospinal fluid erythrocyte burden (CTRED), a marker indicating vascular-CSF barrier disruption and heme toxicity, affects the link between PTAU181 levels and entorhinal cortex atrophy in AD.</p><p><strong>Methods: </strong>We examined 25 observations from 18 patients with AD using a linear mixed effects model. The dependent variable was entorhinal cortex volume, with fixed effects for PTAU, CTRED, and their interaction. Random intercepts accounted for variability within subjects. A cognitively normal (CN) control group was included for comparison.</p><p><strong>Results: </strong>CTRED is significantly associated with reduced entorhinal volume (<i>p</i> = 0.005). A notable interaction between CTRED and PTAU was also found (<i>p</i> = 0.004), suggesting that higher CTRED enhances PTAU's atrophic effects. PTAU alone was not a significant predictor. No significant effects were observed in the CN group, which supports the specificity of the disease.</p><p><strong>Conclusions: </strong>CTRED alters the neurotoxic impact of PTAU on the entorhinal cortex in AD, supporting a multi-hit model of degeneration that involves tau pathology and erythrocyte-derived stress. These findings emphasize the clinical importance of vascular-CSF biomarkers in predicting neurodegeneration and guiding targeted treatments.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Oncological Biomarker Framework Guiding Precision Medicine.","authors":"Reza Bayat Mokhtari, Manpreet Sambi, Faezeh Shekari, Kosar Satari, Roya Ghafoury, Neda Ashayeri, Paige Eversole, Narges Baluch, William W Harless, Lucia Anna Muscarella, Herman Yeger, Bikul Das, Myron R Szewczuk, Sayan Chakraborty","doi":"10.3390/biom15091304","DOIUrl":"10.3390/biom15091304","url":null,"abstract":"<p><p>Cancer remains a major cause of mortality worldwide, driving ongoing innovation in therapeutic strategies. Immunotherapy has transformed cancer care by leveraging the immune system to target tumors, but its effectiveness is limited by tumor heterogeneity, immune resistance, and unpredictable toxicities. Moreover, the absence of robust biomarkers to predict therapeutic response and manage adverse effects remains a significant challenge. Recent advances in biomarker discovery, including liquid biopsy technologies and gut microbiota profiling, are enhancing the precision of immunotherapy and enabling more personalized cancer management. Here, we present a Comprehensive Oncological Biomarker Framework that integrates genetic and molecular testing, imaging, histopathology, multi-omics, and liquid biopsy to generate a molecular fingerprint for each patient. This holistic approach supports individualized diagnosis, prognosis, treatment selection, and response monitoring. Incorporating emerging biomarkers, such as microbiome signatures, further refines patient stratification, guiding the optimization of therapy. By uniting molecular insights with clinical and social factors, this framework aims to address tumor heterogeneity and immune evasion, ultimately improving patient outcomes through precision oncology.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12466961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Anti-Inflammatory Activity of Lipids Extracted from the Most Abundant Cyanobacterial Strains of the Therapeutic Euganean Thermal Muds.","authors":"Micol Caichiolo, Giuliana d'Ippolito, Angela Grazioso, Chiara Rampazzo, Angelica Marchetto, Fabrizio Caldara, Luisa Dalla Valle, Nicoletta La Rocca","doi":"10.3390/biom15091301","DOIUrl":"10.3390/biom15091301","url":null,"abstract":"<p><p>Cyanobacteria are a natural source of bioactive compounds increasingly recognized for their anti-inflammatory properties. In the Euganean Thermal District (Italy), thermal muds, used to cure arthro-rheumatic diseases, are prepared using natural clay and thermal water, resulting in a mature mud characterized by a complex microbial biofilm dominated by Cyanobacteria. Among these, <i>Phormidium</i> sp. ETS-05 has been shown to contribute to the therapeutic properties of the mud, mainly through the production of bioactive compounds such as exopolysaccharides (EPSs) and glycoglycerolipids (GLs). In contrast, the role of biomolecules from <i>Thermospirulina andreolii</i> ETS-09 and <i>Kovacikia euganea</i> ETS-13, also abundant in mature muds but at higher maturation temperatures, has not been investigated. This study focuses on the lipid profiles of these cyanobacteria, cultivated under temperature conditions that mimic their natural environment and that are different for the three species. Lipid extracts were analyzed for GLs classes and fatty acid composition, and their anti-inflammatory potential was assessed in vivo using a zebrafish inflammation model. All extracts showed anti-inflammatory activity with <i>Phormidium</i> sp. ETS-05 displaying the highest lipid content and the most rapid and potent beneficial effect, likely due to the specific composition of its GLs, presenting the greatest abundance of polyunsaturated fatty acids. These findings provide new insights into the biological basis of the therapeutic effects of Euganean muds and emphasize the importance of maturation conditions for cyanobacterial growth and bioactive lipid production.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nature's Synergy: Cellular and Molecular Evaluation of Snail Slime and Its Principal Component, Glycolic Acid, on Keratinocytes, with Preliminary Evidence from Endothelial Cells.","authors":"Muhammad Rashad, Alessia Ricci, Serena Pilato, Amelia Cataldi, Marwa Balaha, Susi Zara","doi":"10.3390/biom15091302","DOIUrl":"10.3390/biom15091302","url":null,"abstract":"<p><p>Snail slime (SS) is a natural secretion rich in bioactive components such as glycoproteins, hyaluronic acid, glycolic acid (GA), and antimicrobial peptides. GA, a key component of SS, is known for its exfoliative properties. This study investigates SS's effects on keratinocytes (HaCaT) and endothelial cells (ECs), comparing its properties to those of GA. HaCaT cell viability and cytotoxicity, ROS release, and inflammation-related signaling (PI3K/Akt/NF-κB and COX-2 gene expression) were assessed. Extracellular matrix (ECM) remodeling was evaluated by gene expression of MMPs. In ECs, a preliminary evaluation of SS's effect was conducted in terms of cell viability and migration. Results demonstrated that SS is well tolerated by keratinocytes whereas GA exhibits cytotoxicity, suggesting that SS's natural composition mitigates GA's adverse effects. SS induced a controlled, brief inflammatory response, via the PI3K/Akt/NF-κB pathway, unlike GA, responsible for stronger and sustained pro-inflammatory events. Additionally, SS, through the upregulation of MMPs, contributes to ECM remodeling. In ECs, SS preserves viability and also enhances migration, thus supporting wound healing. These findings highlight SS's ability to balance pro-inflammatory events, making it a promising candidate for advanced dermatological applications, underscoring SS's potential in modulating key cellular signaling pathways, and supporting its future therapeutic prospects in wound healing.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.","authors":"Alexander Morin, Michael Christie, Eve Damiano, Maria L Maccecchini","doi":"10.3390/biom15091299","DOIUrl":"10.3390/biom15091299","url":null,"abstract":"<p><p>Buntanetap is an orally bioavailable small molecule that has been shown to improve cognitive function in patients with Alzheimer's and Parkinson's diseases and holds promise for use in other neurodegenerative conditions. Until now, a crystalline anhydrate (Form A) has been used in preclinical and clinical studies. However, a novel dihydrate crystal (Form B) was recently discovered, offering improved solid-state stability without compromising its absorption, systemic exposure, and metabolism. We sought to evaluate the pharmacokinetic (PK) profile of Form B and compare it to the well-characterized PK profile of Form A in a series of studies conducted in mice, dogs, and humans. Our data revealed that although the two forms are distinct and do not interconvert, they exhibit comparable PK profiles both within and across species. Consistent with previous reports, Form A and Form B alike reached fast peak plasma concentrations (<2 h), demonstrated efficient partitioning into brain tissue, and were fully cleared by 12 h post-dose. Furthermore, metabolic profiling showed that both forms produced identical PK profiles for the primary metabolites, N1- and N8-norbuntanetap, confirming that Form B retains the established metabolic characteristics of Form A. These findings support the continued development of Form B for future clinical use, as it combines enhanced solid-state stability with a preserved PK profile essential for buntanetap's therapeutic efficacy.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12467374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}