Russian Journal of Bioorganic Chemistry最新文献

{"title":"Ligand-Mediated Conformational Plasticity of the Pore Domain of TRPV6 Ion Channel","authors":"I. I. Veretenenko,&nbsp;V. V. Vantsev,&nbsp;Y. A. Trofimov,&nbsp;R. G. Efremov","doi":"10.1134/S1068162026601643","DOIUrl":"10.1134/S1068162026601643","url":null,"abstract":"<p>TRPV6 is a Ca²⁺-selective ion channel that plays a vital role in calcium homeostasis in the human body, including the absorption of dietary calcium. Dysfunction of TRPV6 can contribute to the development of various diseases, including several types of cancer. Therefore, identifying and studying the molecules involved in the regulation of TRPV6 function is a crucial task in modern pharmacology, requiring a thorough understanding of its mechanisms of action and ligand-mediated regulation at a molecular level. The ion-conducting pore is a key functional domain of TRPV6, which is a conformationally plastic nanotube with a complex structural and hydrophobic organization that is capable of responding to various physical and chemical stimuli. This review provides an overview of recent experimental and computational studies of the TRPV6 pore properties in different conformational states, and its response to various endogenous and exogenous molecular modulators.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Backbone Structure-Conditioned Sequence Design Using Machine Learning-Based Approaches","authors":"I. Yu. Gushchin,&nbsp;A. S. Nikolaev,&nbsp;E. A. Kuznetsova,&nbsp;A. D. Bugrova,&nbsp;A. A. Afanasev,&nbsp;A. A. Remeeva","doi":"10.1134/S1068162026601497","DOIUrl":"10.1134/S1068162026601497","url":null,"abstract":"<p>Rational modification and enhancement of protein function are extremely important both for understanding the fundamental principles of operation of natural macromolecules and for practical applications. Recent flourishing of machine learning-based methods in structural biology led to noteworthy advances in protein structure prediction tasks, which in turn enabled development of versatile protein engineering approaches. Among them, the methods aimed at predicting the sequence that would fold into a conditioned structure proved particularly useful. Here, we review the diversity of these methods, their applications in basic and applied research, and discuss the challenges that remain to be overcome in the future.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Properties of LMNG/CHS Micelles","authors":"Konstantin Mineev,&nbsp;Harald Schwalbe","doi":"10.1134/S1068162026601680","DOIUrl":"10.1134/S1068162026601680","url":null,"abstract":"<p><b>Objective:</b> Reconstituting a membrane protein in a membrane-like environment is an essential factor, determining the relevance of structural data obtained for a membrane protein. Mixtures of lauryl maltose neopentyl glycol (LMNG) with cholesteryl hemisuccinate (CHS) are a recently introduced membrane-like medium with a proven stabilizing effect on membrane proteins of several classes. However, the structure of LMNG/CHS micelles remains underinvestigated. <b>Methods:</b> In the present work, we apply diffusion and nuclear Overhauser effect NMR spectroscopy and the transmembrane domain pf EphA2 as a sensor transmembrane protein to characterize the properties of LMNG/CHS micelles in comparison to other membrane mimetics, including phospholipid bicelles. <b>Results and Discussion:</b> According to the diffusion measurements, CHS addition to LMNG micelles reduces the temperature- and concentration-induced growth of the particles, preventing LMNG from forming non-regular rod-like structures. CHS is evenly distributed within the micelles, with no preference for the protein-adjacent regions. For a model protein, LMNG/CHS provides an environment similar to dodecyl maltoside but distinct from lipid bicelles in terms of lipid-protein contacts. <b>Conclusions:</b> LMNG/CHS is a membrane mimetic that stabilizes membrane proteins, has a defined micellar structure with even CHS distribution, suppresses undesirable rod-like LMNG aggregation, and offers a lipid-protein contact environment different from that of bicelles but similar to dodecyl maltoside.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Mutant Alpha-Subunit Kv1.1(A261T) on the Properties of the Heterotetrameric Channel Kv1.1-Kv1.2","authors":"A. V. Efremenko,&nbsp;I. Dzhumaniiazova,&nbsp;D. V. Abramochkin,&nbsp;I. I. Shmatin,&nbsp;V. N. Korabeynikova,&nbsp;E. V. Kryukova,&nbsp;M. P. Kirpichnikov,&nbsp;A. V. Feofanov,&nbsp;O. V. Nekrasova","doi":"10.1134/S106816202660131X","DOIUrl":"10.1134/S106816202660131X","url":null,"abstract":"<p><b>Objective:</b> Mutation A261T in the Kv1.1 α-subunit of voltage-gated potassium channels Kv1 is associated with episodic ataxia type 1, myokymia, and epileptic syndrome. The mutation enhances the function of homotetrameric Kv1.1 channels, promoting their premature opening and, as a consequence, leading to hyperpolarization of the cell membrane. To clarify the molecular mechanisms underlying the phenotypic manifestation of this mutation in patients, the properties of mutant heterochannels Kv(1.1(A261T)–1.2)₂, which are the main form of presentation of the Kv1.1 α-subunit in the central nervous system, were studied. <b>Methods:</b> Confocal microscopy, the Förster resonance energy transfer method and electrophysiological techniques were used to study the properties of the mutant Kv1.1(A261T) α-subunit, homotetrameric Kv1.1(A261T) channels, as well as heterochannels Kv(1.1(A261T)–1.2)₂ formed by concatemers Kv1.1(A261T)–Kv1.2, which were expressed in mice neuroblastoma Neuro-2a cells. <b>Results and Discussion:</b> It was found that the A261T mutation accelerated the incorporation of homotetrameric channels Kv1.1(A261T) into the plasma membrane of cells. The mutation did not interfere with the channel binding to peptide blockers and did not impair the ability of α-subunits Kv1.1(A261T) to form heterochannels Kv1.1/Kv1.2. The mutant heterochannels Kv(1.1(A261T)–1.2)₂ exhibited a significant decrease in the membrane potential that activated the channels, as well as accelerated activation and deactivation kinetics compared to heterochannels without the mutation. The peptide blockers hongotoxin 1 and Ce4 retained high affinity for mutant heterochannels and significantly reduced currents through these channels. <b>Conclusions:</b> The data obtained suggest that the gain-of-function effect of the A261T mutation is preserved in heterochannels Kv(1.1(A261T) –1.2)₂ but is reduced as compared to homotetrameric channels Kv1.1(A261T). Thus, the altered properties of the mutant heterochannels may underlie the phenotypic manifestations of this mutation, as well as the development of the pathology of the nervous system. High-affinity peptide blockers may facilitate the studies of mutant heterochannels in neurons and the development of therapeutic agents for these types of channelopathies.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fused Imidazo[1,2-a]pyrimidines Containing 1,2,3-Triazoles and Isoxazoles: One-Pot Synthesis, Anticancer, and EGFR-Inhibitory Activities","authors":"Suresh S. Ardhapure,&nbsp;Nilesh B. Chavhan,&nbsp;Sainath L. Shinde,&nbsp;Shivraj B. Sirsat","doi":"10.1134/S1068162025602824","DOIUrl":"10.1134/S1068162025602824","url":null,"abstract":"<p><b>Objective:</b> A series of imidazo[1,2-<i>a</i>]pyrimidine derivatives containing 1,2,3-triazoles and isoxazoles were synthesized, and their anticancer activity against lung cancer was evaluated. <b>Methods:</b> The one-pot reaction of (<i>Z</i>)-<i>N</i>-(4-iodobut-3-yn-2-ylidene)-1<i>H</i>-imidazol-2-amine <b>III</b> with various nitrile oxides and aryl azides, proceeding <i>via</i> <i>in situ</i> generated 4-iodoisoxazoles and 5-iodotriazoles, yielded the final fused isoxazoles and triazoles. The anticancer activity of the synthesized derivatives was determined using the MTT assay. <b>Results and Discussion:</b> The structures of the newly synthesized compounds were confirmed by ¹H, ¹³C NMR, and mass spectrometry. Among the derivatives, compounds <b>IVe</b> and <b>IVd</b> exhibited potent activity against the A549 cell line with IC₅₀ values of 4.43 ± 0.36 and 6.52 ± 0.63 μM, respectively. They also demonstrated significant EGFR inhibitory activity with IC₅₀ values of 0.67 ± 0.05 and 0.89 ± 0.07 μM, respectively. <b>Conclusions:</b> A new series of fused imidazo[1,2-<i>a</i>]pyrimidines containing 1,2,3-triazoles and isoxazoles was developed and investigated for <i>in vitro</i> activity against lung cancer. Compounds <b>IVe</b> and <b>IVd</b> showed promising results in both cytotoxicity and EGFR inhibition assays. These scaffolds, with further structural optimization, hold potential as candidates for future cancer therapeutics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions with Alexander Arseniev at the ETH Zürich and Thereafter","authors":"Gerhard Wagner","doi":"10.1134/S1068162026601357","DOIUrl":"10.1134/S1068162026601357","url":null,"abstract":"<p>In this commemorative article, Gerhard Wagner recalls his scientific interactions with Alexander Arseniev during his time at ETH Zürich and thereafter. The narrative focuses on their collaborative NMR project to determine the solution structure of rabbit liver metallothionein-2, a protein with no prior crystal or solution structure. Key challenges included correcting errors in the published amino acid sequence and determining how seven metal ions coordinate with twenty cysteine residues. By replacing Zn²⁺ with ¹¹³Cd²⁺ and applying newly developed inverse-detection heteronuclear correlation experiments, crucial cadmium–cysteine connectivities were obtained. Arseniev successfully used Distance Geometry algorithms to calculate the three-dimensional fold, revealing two domains with metal clusters forming the protein’s hydrophobic core. The article also describes the comparison with an initially conflicting crystal structure, leading to a joint publication in PNAS, as well as personal meetings between Wagner and Arseniev in Russia and the United States.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Chromen–THP Hybrids as Dual Anticancer and Antioxidant Agents: In Silico and In Vitro Evaluation","authors":"Ansari Altamash Shakeel Ahmad,&nbsp;Mirza Shahid Baig,&nbsp;J. N. Sangshetti,&nbsp;Yasar Qazi","doi":"10.1134/S1068162025602897","DOIUrl":"10.1134/S1068162025602897","url":null,"abstract":"<p><b>Objective:</b> This study evaluates the dual anticancer and antioxidant activities of the synthesized hybrids in both <i>in vitro</i> and <i>in silico</i> models. <b>Methods:</b> A series of chromen–tetrahydropyrimidine hybrids (<b>4a–4f</b> and <b>6a–6f</b>) were synthesized <i>via</i> a one-pot Biginelli reaction using oxalic acid as a catalyst, combining substituted acetoacetates, aromatic aldehydes, and urea/thiourea. Characterization was performed using IR, NMR, and mass spectrometry. Anticancer activity was assessed against MCF-7 and MDA-MB-231 breast cancer cell lines using the SRB assay, while antioxidant activity was measured <i>via</i> the DPPH assay. <i>In silico</i> ADME properties were predicted using ADMETlab 2.0. Network pharmacology identified potential targets and pathways, supplemented by molecular docking and simulation studies to evaluate binding interactions and stability. <b>Results and Discussion:</b> Compounds <b>4d</b>, <b>4e</b>, <b>4f</b>, <b>6b</b>, and <b>6f</b> showed potent cytotoxicity with GI₅₀ values &lt;10 μg/mL in both cell lines, with <b>6c</b> selectively targeting MDA-MB-231. Compounds <b>4a</b>, <b>4b</b>, <b>6b</b>, and <b>6f</b> exhibited strong antioxidant activity, with IC₅₀ values comparable to that of ascorbic acid (45.63 ± 0.20 μg/mL). Network pharmacology identified the top two hub genes STAT3 and AKT1, and KEGG pathway analysis revealed pathways in cancer, PI3K-Akt, and MAPK signaling as key contributors to anti-breast cancer effects. Molecular docking revealed high binding affinities, with <b>4d</b> (−8.7 kcal/mol, AKT1) and <b>6b</b> (−8.1 kcal/mol, STAT3). Molecular dynamic simulations confirmed stable protein-ligand complexes with minimal fluctuations. ADME analyses indicated favorable pharmacokinetics and low toxicity. <b>Conclusions:</b> These hybrids show promise as dual anticancer and antioxidant agents, warranting further development for breast cancer therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into Novel Tetrazole-Encompassing 1,2,3-Triazoles as Antimicrobial and Anti-TB Agents: Synthesis, ADME-Tox, and In Silico Molecular Docking","authors":"P. S. Reddy,&nbsp;T. Sekhar,&nbsp;P. Thriveni,&nbsp;A. T. Rao,&nbsp;T. Giridhar,&nbsp;V. A. Kumar,&nbsp;G. Srinivasulu,&nbsp;P. V. V. N. Kishore","doi":"10.1134/S1068162025601351","DOIUrl":"10.1134/S1068162025601351","url":null,"abstract":"<p><b>Objective:</b> The 1,2,3-triazole nucleus exhibits various biological activities and is an integral part of many naturally occurring and synthetic heterocyclic derivatives. This study aims to synthesise and evaluate the antimicrobial and anti-TB efficacy of a series of 1,2,3-triazole-linked tetrazole derivatives as potential therapeutic agents against antibiotic-resistant bacteria and TB. <b>Methods:</b> A new kind of 1,2,3-triazolyl-tetrazoles bearing cycloheptapyridinone conjugates was synthesised using click chemistry. HRMS spectrometry, FT-IR, and NMR (¹H and ¹³C) were all utilised to characterise each of the recently generated scaffolds. The antimicrobial and antitubercular activities of the newly synthesised hybrids were assessed by minimum inhibitory concentration (MIC) measurements, and computational studies were conducted using AutoDock Tools. <b>Results and Discussion:</b> All synthesised compounds possess an active 1,2,3-triazole moiety in their structure, and the cycloheptapyridinone nucleus has a hydroxy group at the 9th position. According to the results obtained, tetrazole compounds <b>VIIId</b>, <b>VIIIh</b>, and <b>VIIIi</b> were particularly effective at inhibiting the growth of all tested bacteria, with MIC values ranging from 0.983 to 16.762 μg/mL; compared to moxifloxacin (MXF) (2.191 to 10.01 μg/mL). The highest antitubercular properties were shown by compounds <b>VIIId</b> and <b>VIIIi</b>, with MIC values of 2.20 and 2.10 μg/mL against the H37Rv strain. Furthermore, compounds <b>VIIIb</b>, <b>VIIIh</b>, and <b>VIIIi</b> demonstrated better binding energies and inhibition constants for <i>K. pneumoniae</i> and <i>Mycobacterium tuberculosis</i> (PDB ID: 6JYY and 1DF7). <b>Conclusions:</b> The synthesised cycloheptapyridinone compounds present a promising basis for the development of biosafe and pharmacologically active scaffolds for novel therapeutics.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modification-Driven Enhancement of Antimicrobial Activity in Cellulose-Based Materials: Trends and Applications (2021–2025)","authors":"Mohammed Sanad Alhussaini,&nbsp;AbdulRahman Abdulla Ibrahim Alyahya,&nbsp;Abdullah Abdulrahman Al-Ghanayem","doi":"10.1134/S1068162025602964","DOIUrl":"10.1134/S1068162025602964","url":null,"abstract":"<p>Cellulose, the most abundant and renewable natural polymer, has emerged as a promising platform for developing sustainable antimicrobial materials. Recently, extensive research has focused on cellulose to impart and enhance its antimicrobial properties through diverse strategies. This review presents a comprehensive analysis of recent advances in the chemical, physical, and biological modification of cellulose aimed at boosting its antimicrobial efficacy. Key approaches include the incorporation of metal and metal oxide nanoparticles, surface grafting of cationic moieties, covalent attachment of antimicrobial agents, and blending with naturally derived biocides such as chitosan and essential oils. Mechanisms underlying antimicrobial action, including membrane disruption, oxidative stress, and enzyme inhibition, are also discussed. The review further explores application-specific innovations in fields such as wound healing, medical textiles, food packaging, water purification, and smart coatings. By providing a critical overview of modification-driven enhancement strategies, this review aims to guide future research in designing multifunctional, eco-friendly, and high-performance cellulose-based antimicrobial materials.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147738180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Machine Learning Screening and Functional Validation of Autophagy-Related Genes in Osteoporosis","authors":"Jie Shi,&nbsp;Yongxian Wan","doi":"10.1134/S1068162025603039","DOIUrl":"10.1134/S1068162025603039","url":null,"abstract":"<p><b>Objective:</b> This study aimed to identify key autophagy-related genes involved in osteoporosis using machine learning algorithms. <b>Methods:</b> Differential expression analysis between osteoporotic and control groups was performed using DESeq2. Candidate genes were obtained by intersecting the differentially expressed genes with a reference set of autophagy-related genes. Subsequently, LASSO regression, support vector machine, and random forest algorithms were applied to screen for characteristic genes. The overlapping genes resulting from all three methods were designated as feature genes. The <i>in vitro</i> expression of the feature genes was validated using RT-qPCR and western blot, and their functional roles in osteoblast differentiation and mineralization were assessed. <b>Results and Discussion:</b> Differentially expressed genes between the osteoporosis and control groups were identified based on adjusted <i>p</i>-values and |log₂(fold change)|. Candidate genes were obtained by intersection with autophagy-related genes. Osteoporosis feature genes were screened from the candidate gene set using three well-recognized machine-learning algorithms. This approach yielded four feature genes: <i>ADAM12</i>, <i>GZMB</i>, <i>SERPINF1</i>, and <i>TRIM6</i>. In the osteoporosis cell model, <i>ADAM12</i> and <i>SERPINF1</i> were downregulated, whereas <i>GZMB</i> and <i>TRIM6</i> were upregulated. ROC curve analysis indicated that all four feature genes exhibited strong discriminatory performance between osteoporotic and control samples (AUC &gt;0.9), suggesting that the model possesses robust diagnostic ability. Functional experiments demonstrated that <i>TRIM6</i> is involved in the regulation of osteoblast differentiation and mineralization. A gene regulatory network analysis revealed that EGR1, MAZ, and FOXA2 simultaneously regulate <i>ADAM12</i>, <i>SERPINF1</i>, and <i>TRIM6</i>. Drug sensitivity analysis indicated that increased <i>TRIM6</i> expression correlates with sensitization to A-804598, istradefylline, SZ4TA2, sildenafil, MI-2, erismodegib, MK-0752, and necrostatin-7. <b>Conclusions:</b> Using machine learning algorithms, this study identified four osteoporosis-related autophagy-related feature genes: <i>ADAM12</i>, <i>SERPINF1</i>, <i>GZMB</i>, and <i>TRIM6</i>, which may serve as potential diagnostic markers. <i>TRIM6</i> expression was found to be positively correlated with individual sensitivity to A-804598, istradefylline, SZ4TA2, and sildenafil, among others. Furthermore, <i>TRIM6</i> was shown to participate in osteoblast differentiation and mineralization.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147720936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}