IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70589

Michela Aliberti, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro

{"title":"Beyond Inhibition: Emerging Approaches in Ubiquitin–Proteasome-Mediated Protein Degradation for Precision Targeting","authors":"Michela Aliberti, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro","doi":"10.1002/cbic.70589","DOIUrl":"10.1002/cbic.70589","url":null,"abstract":"Targeted protein degradation (TPD) represents an emerging paradigm in drug discovery, capable of overcoming the limitations of traditional therapeutic strategies based on protein inhibition. Exploiting the ubiquitin–proteasome system (UPS), TPD allows the selective elimination of pathologically relevant proteins. The most established approaches in TPD are proteolysis-targeting chimeras (PROTACs) and molecular glue (MG) chemical degraders, which feature distinct molecular architectures and mechanisms of action. Although these approaches have proven highly effective in promoting the selective degradation of target proteins, their use is often accompanied by critical issues related to tissue selectivity and biodistribution. To overcome these limitations, advanced strategies have been developed in recent years that exploit endogenous and exogenous triggers, such as antibody–PROTAC conjugates and PROTAC prodrugs that can be activated by enzymes, redox conditions, hypoxia, light, or radiotherapy, allowing for more precise spatial and temporal control of degradation. Alternative approaches, such as hydrophobic tagging, further expand the available repertoire, circumventing the E3 ligase dependency inherent to PROTAC systems for protein destabilization and confirming the versatility of the TPD platform. In this review, an overview of the most effective and promising approaches in TPD is reported, focusing on the most recent technological advances and reporting key case studies.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monitoring Enzyme Activity on the Surface of a Self-Referenced Near-White Light Emitting Assembly of Atomic Clusters 自参考近白光原子团簇组件表面酶活性的监测。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70595

Oushnik Sengupta, Santanu Dolai, Srestha Basu

{"title":"Monitoring Enzyme Activity on the Surface of a Self-Referenced Near-White Light Emitting Assembly of Atomic Clusters","authors":"Oushnik Sengupta, Santanu Dolai, Srestha Basu","doi":"10.1002/cbic.70595","DOIUrl":"10.1002/cbic.70595","url":null,"abstract":"Sensitive detection of protease activity in complex biological environments remains challenging due to signal instability, background interference, and the lack of internal calibration. Here, we report a self-referenced, white-light–emitting surface defect-engineered nanocluster assembly for selective and ratiometric detection of proteinase K activity and inhibition. Manganese-doped, zinc-mediated gold nanocluster (Zn Au NC) assemblies functionalized with bovine serum albumin (BSA) generate tricolor emission from BSA, the nanocluster core, and Mn2+, producing near-white-light fluorescence that serves as an intrinsic internal reference. Proteinase K induces coordinated spectral changes, including enhanced and blueshifted BSA emission with simultaneous quenching of Zn Au NC and Mn2+ emissions, resulting in systematic chromaticity shifts and a robust ratiometric response. Mechanistic studies attribute these changes to proteolytic cleavage of BSA and disruption of the nanocluster assembly, corroborated by circular dichroism measurements. The platform exhibits high selectivity for proteinase K, enables inhibitor detection, and performs reliably in fetal bovine serum. This self-calibrated nanocluster platform provides a versatile strategy for enzyme-responsive sensing with potential applications in biochemical diagnostics and inhibitor screening.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Beyond Thiol-Dependent Cyclization of Peptide Libraries: Assessing a Photochemical Alternative 超越硫醇依赖的肽库环化：评估光化学替代品。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70578

Alessia Procentese, Maria De Fenza, Ornella Maglio, Angela Lombardi, Marco Chino

{"title":"Beyond Thiol-Dependent Cyclization of Peptide Libraries: Assessing a Photochemical Alternative","authors":"Alessia Procentese, Maria De Fenza, Ornella Maglio, Angela Lombardi, Marco Chino","doi":"10.1002/cbic.70578","DOIUrl":"10.1002/cbic.70578","url":null,"abstract":"Cyclic peptides are powerful scaffolds for chemical biology and drug discovery. Genetically encoded display (phage, ribosome, mRNA, and yeast) enables high-throughput screening of peptide libraries. Yet expanding their accessible chemical space depends not only on library size but also on the cyclization chemistry, which selects the conformations the library samples and makes linkage choice a primary design variable. Cyclization most often relies on cysteine through disulfides, thiol-reactive linkers, or metal-thiolate bonds. Enzymatic head-to-tail ligation and noncanonical amino acids (ncAAs) provide cysteine-free macrocyclization through amide bonds, but each imposes practical limits such as motif constraints or reliance on genetic code expansion. In this perspective, we examine photoinduced aromatic crosslinking as a complementary, cysteine-independent strategy. Recent fluorotryptophan photochemistry shows that irradiation drives diaryl bond formation between fluorinated tryptophan and proximal phenylalanine or tyrosine, generating intrinsically fluorescent macrocycles and enabling an optical readout of cyclization yield. Fluorotryptophan is a conservative modification that can be introduced at native Trp codons, which may avoid the genetic code expansion. Antimicrobial peptides offer a demanding test case: their function depends on backbone rigidity, amphipathic face presentation, and membrane interaction, all of which an aromatic crosslink could influence.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coiled Coils as a Programmable Platform for Computational Biosensor Design 卷绕线圈作为计算生物传感器设计的可编程平台。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70585

Paul Kluge, Faezeh Shabani, Sibylle Gemming, Georg Künze

{"title":"Coiled Coils as a Programmable Platform for Computational Biosensor Design","authors":"Paul Kluge, Faezeh Shabani, Sibylle Gemming, Georg Künze","doi":"10.1002/cbic.70585","DOIUrl":"10.1002/cbic.70585","url":null,"abstract":"Coiled coils are a versatile class of α-helical protein motifs characterized by recurring sequence patterns that direct their assembly into defined oligomeric bundles and underpin a wide range of biological functions. The well-established sequence-structure relationships governing coiled-coil formation enable predictive control over stability, specificity, and oligomerization state, making them attractive and chemically tractable building blocks for biosensor design in applications ranging from single-molecule detection to synthetic biochemical circuits and functional nanomaterials. After revisiting the theoretical foundations of coiled-coil architecture, this review outlines strategies to engineer programmable binding interfaces that can be rationally tuned to generate orthogonal, high–affinity interaction pairs, enabling flexible and modular biosensor platforms. Particular emphasis is placed on recent advances in computational and data-driven design approaches, including machine-learning and AI-based strategies, alongside established rational and empirical methods for coiled-coil construction. These complementary design principles underpin the development of coiled-coil-based biosensors and are discussed together with selected application examples to illustrate how engineered coiled-coil interactions support sensitive and specific molecular recognition as well as switchable control in synthetic biology and chemical biology. Overall, this review highlights coiled coils as programmable, stable, and highly designable scaffolds at the interface of molecular engineering, computation, and chemical biology.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

On the Need to Revise the Amyloid Cascade Hypothesis 论修改淀粉样蛋白级联假说的必要性。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70583

David B. Teplow, Jevgenij A. Raskatov

{"title":"On the Need to Revise the Amyloid Cascade Hypothesis","authors":"David B. Teplow, Jevgenij A. Raskatov","doi":"10.1002/cbic.70583","DOIUrl":"10.1002/cbic.70583","url":null,"abstract":"Seven million people in the USA are estimated to suffer from Alzheimer’s disease (AD), a number expected to double by 2050. Patient care costs >$350 billion/year now but will exceed $1 trillion by 2050, bankrupting our economy. Tremendous progress in understanding and treating AD has been made over the past 4 decades, yet, after >400 clinical trials, no efficacious AD treatments exist. The amyloid cascade hypothesis (ACH), the leading disease model, holds that amyloid β (Aβ) initiates a cascade leading to disease. Alternative processing cleaves APP in the middle of Aβ, producing the C-terminal fragment, p3. Simply put, if the ACH is true, no Aβ means no disease because p3 is believed soluble, non-amyloidogenic, and nontoxic. However, recent studies have shown this to be untrue. In fact, p3 is more amyloidogenic than Aβ, and is neurotoxic. It also forms mixed aggregates with Aβ that have distinct structures and neurotoxicities. ACH has led the AD field to largely ignore these facts. Here, we provide an integrated perspective on how this has come about and urge expansion of the ACH to consider the possible roles of p3 in AD and to refer to it as Amyloid α (Aα), to better reflect its nature.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70583","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Visualizing Telokin-Dependent Regulation of Myosin Filaments by Electron Microscopy 用电镜观察肌凝蛋白丝的端粒依赖性调控。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70584

Poushali Mitra, Rohit Singh, Kaushiki Tiwari, Prince Tiwari

{"title":"Visualizing Telokin-Dependent Regulation of Myosin Filaments by Electron Microscopy","authors":"Poushali Mitra, Rohit Singh, Kaushiki Tiwari, Prince Tiwari","doi":"10.1002/cbic.70584","DOIUrl":"10.1002/cbic.70584","url":null,"abstract":"Smooth muscle myosin (SmM) is the primary force-generating motor protein in smooth muscle cells. It undergoes conformational transitions between a compact, inactive folded state (10S) and an extended, filament-forming state (6S). Telokin (Tkn), the noncatalytic C-terminal domain of myosin light chain kinase (MLCK), has been implicated in regulating myosin filament stability. However, the molecular basis of its interaction with SmM remains incompletely understood. In this study, we have employed recombinant human Tkn to investigate its role in SmM filament assembly. Circular dichroism spectroscopy, fluorescence spectroscopy, and chromatographic studies were used to confirm the structural integrity and functional activity of the purified proteins. Remarkably, the presence of Tkn promoted myosin filament assembly even with ATP, a condition that typically favors the folded 10S conformation and inhibits filament formation. Transmission Electron Microscope (TEM) micrographs of the resulting filaments showed predominantly non-bipolar filaments that closely resembled the native side-polar smooth muscle thick filaments. Despite sequence variations within the acidic C-terminal region, human Tkn efficiently induced filament assembly of avian SmM, indicating conservation of the underlying filament-promoting mechanism across species. Collectively, these findings provide direct experimental evidence that Tkn acts as a structural regulator of filament assembly and stability. This offers new insights into the mechanisms governing smooth muscle contractility.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Catalytic DNA for Precision Diagnostics: DNAzyme-Based Approaches to Single-Nucleotide Polymorphism Detection 催化DNA用于精确诊断：基于dnazyme的单核苷酸多态性检测方法。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70591

Marah Alkhalili, Saqer Al Abdullah, Farbod Ebrahimi, Kristen Dellinger

{"title":"Catalytic DNA for Precision Diagnostics: DNAzyme-Based Approaches to Single-Nucleotide Polymorphism Detection","authors":"Marah Alkhalili, Saqer Al Abdullah, Farbod Ebrahimi, Kristen Dellinger","doi":"10.1002/cbic.70591","DOIUrl":"10.1002/cbic.70591","url":null,"abstract":"Single-nucleotide polymorphisms (SNPs) are the most abundant form of human genetic variation and serve as important biomarkers in disease risk assessment, therapeutic stratification, and precision medicine. Yet accurate detection of low-abundance SNPs in complex biological samples remains difficult with many conventional genotyping methods, which often rely on sophisticated instrumentation and show limited tolerance to matrix interference. DNAzyme-based biosensors offer a promising alternative by coupling programmable nucleic acid recognition with catalytic signal generation under isothermal conditions. This review highlights recent advances in DNAzyme-based SNP detection across optical, electrochemical, and amplification-assisted formats, including fluorescence, colorimetric, chemiluminescent, rolling circle amplification, loop-mediated isothermal amplification, hybridization chain reaction, and catalytic hairpin assembly strategies. We also discuss molecular design principles that enhance single-base discrimination, such as binding-arm engineering, cofactor tuning, and computational sequence design. Finally, we outline current limitations, including nuclease susceptibility, temperature dependence, and performance in complex sample matrices, and consider emerging opportunities for DNAzyme-enabled SNP analysis in point-of-care diagnostics, personalized medicine, and large-scale genomics.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

RNA Aptamer-Enabled Development of Heterobifunctionals That Chemically Induce RNA-FKBP12 Ternary Complexes 利用RNA适体开发化学诱导RNA- fkbp12三元配合物的异双功能物。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70597

James E. Melnyk, Maggie Chen, Jennifer E. Hurtig, Elijah Lee, Matheus Pires de Carvalho, Jonathan D. Mortison

{"title":"RNA Aptamer-Enabled Development of Heterobifunctionals That Chemically Induce RNA-FKBP12 Ternary Complexes","authors":"James E. Melnyk, Maggie Chen, Jennifer E. Hurtig, Elijah Lee, Matheus Pires de Carvalho, Jonathan D. Mortison","doi":"10.1002/cbic.70597","DOIUrl":"10.1002/cbic.70597","url":null,"abstract":"Limitations in the druggability of challenging protein targets, coupled with recognition of the diverse roles of noncoding RNAs in cellular regulation and disease have spurred interest in RNA as a druggable macromolecule. The rapidly emerging field of RNA-targeted small-molecule therapeutics is now exploring induced proximity mechanisms in the form of RNA-targeting chimeras that recruit effector proteins to catalyze RNA decay. Inspired by “molecular glue” natural products such as rapamycin and cyclosporin A, which induce protein–protein interactions to sterically modulate protein function, we propose the new application of immunophilin recruitment to alter RNA function. Here in, we report the design and characterization of heterobifunctional molecules that induce highly cooperative RNA-FKBP12 ternary complexes and describe efforts to assess their impact on RNA metabolism. We also evaluate applications and report off-target liabilities associated with the chosen RNA ligand for our heterobifunctional series. Finally, we discuss the challenges faced and highlight opportunities for future success in the RNA space.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of POPG and Cholesterol on Freeze–Thawing Mediated Content Exchange and Transcription in Giant Unilamellar Vesicles POPG和胆固醇对巨型单层小泡冻融介导的内容物交换和转录的影响。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70594

Tsubasa Yamashina, Masaya Oki, Gakushi Tsuji

{"title":"Effects of POPG and Cholesterol on Freeze–Thawing Mediated Content Exchange and Transcription in Giant Unilamellar Vesicles","authors":"Tsubasa Yamashina, Masaya Oki, Gakushi Tsuji","doi":"10.1002/cbic.70594","DOIUrl":"10.1002/cbic.70594","url":null,"abstract":"Freeze–thaw (F/T)-induced content mixing between artificial cells enables efficient exchange of encapsulated components. However, F/T treatment is often accompanied by vesicle rupture and content loss, and the effects of membrane composition on fusion and reaction efficiency remain unclear. Here, we investigated how cholesterol and the negatively charged phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (POPG) influence giant unilamellar vesicle (GUV) stability, content mixing, and transcriptional activity after F/T treatment. Cholesterol-containing GUVs exhibited increased vesicle loss and reduced content mixing after F/T treatment. In contrast, POPG markedly improved GUV recovery and suppressed vesicle loss, even in the presence of cholesterol. Membranes containing 20 mol% POPG and 20 mol% cholesterol maintained high cargo retention and efficient content mixing. When DNA-containing liposomes were fused with transcription-reagent-containing liposomes through F/T treatment, this membrane composition also yielded the highest transcriptional activity. Notably, although the combination of POPG and cholesterol inhibited transcription in intact GUVs, it showed the highest transcriptional activity following F/T-mediated content mixing. These findings demonstrate that the effects of membrane composition on encapsulated biochemical reactions depend strongly on whether the reaction components are initially coencapsulated or brought together through F/T-mediated content exchange.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Shikonin: From Biosynthesis and Pharmacological Mechanisms to Translational Safety and Drug Delivery 紫草素：从生物合成和药理机制到转化安全性和给药。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-11-05 DOI: 10.1002/cbic.70586

Namini Joshi, Prabhakar Semwal, Balwant Rawat, Ravendra Kumar, Mozaniel Santana de Oliveira, Nishant Rai, Janhvi Mishra Rawat

{"title":"Shikonin: From Biosynthesis and Pharmacological Mechanisms to Translational Safety and Drug Delivery","authors":"Namini Joshi, Prabhakar Semwal, Balwant Rawat, Ravendra Kumar, Mozaniel Santana de Oliveira, Nishant Rai, Janhvi Mishra Rawat","doi":"10.1002/cbic.70586","DOIUrl":"10.1002/cbic.70586","url":null,"abstract":"Shikonin (SHK) is a red naphthoquinone produced mainly in the roots of Boraginaceae species and has been investigated for anticancer, anti-inflammatory, antimicrobial, neuroprotective, cardioprotective, hepatoprotective, and wound-healing activities. This review critically integrates botanical sources and biosynthesis with pharmacological mechanisms, preclinical evidence, safety, and delivery strategies. Across cancer models, SHK converges on redox imbalance and regulated cell-death programmes, including apoptosis, cell-cycle arrest, autophagy, necroptosis, ferroptosis, and immunogenic cell death, while modulating NF-κB, MAPK, PI3K/Akt, and related signalling networks. However, the evidence is dominated by heterogeneous in vitro experiments and small-animal studies, with limited pharmacokinetic standardisation, incomplete assessment of selectivity toward diseased versus normal tissues, and almost no robust clinical evaluation. Poor aqueous solubility, chemical and photochemical instability, rapid metabolism, route-dependent exposure, and a context-dependent therapeutic window remain central translational barriers. Liposomes, polymeric micelles, nanoparticles, nanogels, nanoemulsions, and ligand- or stimulus-responsive systems can improve dispersion, tissue accumulation, controlled release, and combination therapy; nevertheless, their long-term safety, manufacturing reproducibility, and comparative advantage over free SHK require rigorous validation. SHK should therefore be regarded as a mechanistically versatile therapeutic lead rather than a clinically established treatment. Translation will depend on exposure–response studies, standardised formulations, clinically relevant models, and well-designed human trials.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 21","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149331820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ChemBioChem最新文献