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The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.

As an important means of modern cancer treatment, targeted therapy has significant efficacy, but cardiac toxicity cannot be ignored. From subclinical myocardial injury to severe heart failure (HF), it poses significant challenges to the long-term survival and quality of life of patients. This article summarizes the impact of targeted therapy drugs on cardiac function and their mechanisms, including cardiomyocyte damage, myocardial hypertrophy, and HF, and conducts in-depth research into potential molecular mechanisms. These include direct cardiomyocyte damage through targeted pathway inhibitio

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… Targeted protein modification (TPM) inhibitor TPM is a general term that encompasses many tools and methods required for using bifunctional reagents to induce TPMs, where the most famous TPM mechanism is proteolysis-targeting chimera-mediated protein ubiquitination, and drug discovery has gone beyond …

Knowledge-map and bibliometric analysis of scientific research on FDA-approved Chimeric Antigen Receptor T cell products (2015-2024).

BackgroundChimeric Antigen Receptor T cell (CAR-T) therapy is a groundbreaking, personalized immunotherapy that genetically engineers patient or donor-derived T cells to recognize and eliminate cancer cells. The U.S FDA has approved six CAR-T cell products in the past decade.ObjectiveGiven their clinical success and scientific novelty, this study aimed to map the research landscape surrounding the FDA-approved CAR-T cell therapies using bibliometric and knowledge mapping analysis.MethodsA comprehensive title/abstract search was conducted in Scopus database for documents published between 2015

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… Is it a chimera? A systematic review of the economic evaluations of CAR-T cell therapy - an update. Expert Rev Pharmacoecon Outcomes Res. 2023;23(6):625–50. PubMed PMID: 37288738. 87. Furzer J, Gupta S, Nathan PC, Schechter T, Pole JD, Krueger J, et al. …

Computational Drug Repurposing Across the Multiple Myeloma Spectrum: From MGUS to MM.

Background/objectivesMultiple myeloma (MM) is a challenging, B cell malignancy characterised by the uncontrolled proliferation of plasma cells within the bone marrow. Despite significant advances in treatment options nowadays, MM remains an incurable malignancy, with the majority of patients succumbing to the disease. MM develops from a pre-malignant state known as monoclonal gammopathy of unknown significance (MGUS), which then has the potential to evolve either into smouldering (asymptomatic) multiple myeloma (SMM) or into MM. Since novel drug discovery takes years to reach the clinic, drug

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… Radanamycin, a macrocyclic chimera of radicicol and geldanamycin. Bioorganic Med. Chem. Lett. 2006;16:2459–2462. doi: 10.1016/j.bmcl.2006.01.086. 39. Soga S., Shiotsu Y., Akinaga S., Sharma S.V. Development of Radicicol Analogues. Curr. …

Dawn of CAR-T cell therapy in autoimmune diseases.

AbstractChimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy hold

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… Redirecting mouse CTL against colon carcinoma: Superior signaling efficacy of single-chain variable domain chimeras containing TCR-zeta vs Fc epsilon RI-gamma. J Immunol 2001;166:182–187. doi: 10.4049/jimmunol.166.1.182. 83. Wu W Zhou Q Masubuchi T Shi X Li H Xu X, et al. …

Лизат парабасероид дистазонис предотвращает серьезные формы экспериментального аутоиммунного энцефаломиэлита, модифицируя примитивную реакцию клеток Т.

Микробиота кишечника влияет на реактивность иммунной системы, а парабактероид дистасонис появился как антивоспалительная комменза. Здесь мы изучили, может ли ли его лизат предотвратить сильные формы нейроинфламмации в экспериментальном аутоиммунном энцефаломиелите (EAE) у мышей и как эта превентивная стратегия влияет на кишечную микробиоту и иммунную реакцию. Лизат анаэробной культуры P. distasonis (Pd лизат) был в устной форме подан мышам C57BL/6 в четырех еженедельных дозах. Неделю спустя EAE был вызван, и через три недели после вводного курса была проведена оценка степени заболеваемости. Фе

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… UCHIME improves sensitivity and speed of chimera detection . Bioinformatics . ( 2011 ) 27 : 2194–200 . doi: 10.1093/bioinformatics/btr381 PMC3150044 21700674 32 Quast C Pruesse E Yilmaz P Gerken J Schweer T Yarza P . …

A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.

The prolonged and intricate history of oncological treatments has transitioned significantly since the introduction of chemotherapy. Substantial therapeutic benefits in cancer therapy have been achieved by the integration of conventional treatments with molecular biosciences and omics technologies. Human epidermal growth factor receptor, hormone receptors, and angiogenesis factors are among the established therapies in tumor reduction and managing side effects. Novel targeted therapies like KRAS G12C, Claudin-18 isoform 2 (CLDN18.2), Trophoblast cell-surface antigen 2 (TROP2), and epigenetic r

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… PROTACs (proteolysis-targeting chimeras) highlight a novel strategy of denaturing key oncogenic proteins rather than inhibiting, leading to overcoming resistance caused by protein overexpression [ 196 ]. …

The Development of Novel Therapies for Chronic Lymphocytic Leukaemia in the Era of Targeted Drugs.

Over the past decade, chronic lymphocytic leukaemia (CLL) treatment has shifted from chemoimmunotherapy to targeted oral agents, predominantly Bruton's tyrosine kinase inhibitors (BTKis) and the BCL-2 inhibitor venetoclax. These therapies have significantly improved outcomes and are now established as first-line treatment options. However, CLL remains incurable, and resistance or intolerance to both drug classes (double-refractory disease) is an emerging challenge. This has driven the development of novel therapeutic strategies, including non-covalent BTKis such as pirtobrutinib and nemtabruti

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… Abbreviations: AE—adverse event; AF—atrial fibrillation; BTK—Bruton tyrosine kinase; CLL—chronic lymphocytic leukemia; CR—complete response; IKZF—IKAROS family zinc finger; NHL—non-Hodgkin lymphoma; ORR—overall response rate; PROTAC—Proteolysis-Targeting Chimera, RR—relapsed/refractory; SLL—small lymphocytic … It was designed as a chimeric degrader to specifically target and degrade BTK using a proprietary Protein–Protein Interaction Targeting Chimeras (PPI-TAC) platform by Accutar Biotech. …

Current trends in theranostic applications of extracellular vesicles in cancer.

BackgroundExtracellular vesicles (EVs) play an integral role in cancer biology, influencing tumor progression, metastasis, and tumor microenvironment. Due to their distinctive molecular composition, including proteins, nucleic acids, and lipids, EVs present a promising candidate for cancer diagnostics and precision therapeutics.MethodsThis review was conducted by looking up recent studies obtained through PubMed, Scopus, and Web of Science databases using targeted keywords such as "Extracellular Vesicles," "Cancer Therapy," "Biomarkers," "Exosomes," "Tumor Microenvironment," and "Precision Med

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… Proteolysis-targeting chimeras (PROTACs) serve as a new therapeutic approach to target select pathogenic proteins through hijacking the ubiquitin-proteasome system for protein breakdown ( 206 , 207 ). …

Multiple Myeloma Therapy: Emerging Trends and Challenges.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergenc

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… Proteolysis-Targeting Chimera Proteolysis-targeting chimera (PROTAC) is a class of bi-functional degrader molecules that have designed to selectively target and then degrade intractable cellular proteins via activation of the ubiquitin–proteasome system. …

Passive Monoclonal and Polyclonal Antibody Therapies

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… Abciximab c7Ec Fab ReoPro FDA 1994 EU 1995 (country-specific approval) Human-murine chimera Recombinant monoclonal IgG1 Fab Procedure modification High-risk coronary intervention Platelet aggregation inhibitor Intravenous Platelet glycoprotein IIb/IIIa receptor (CD41 7E3)/Intergrin α-IIb Abituzumab DI17E6 … GUCY2C) Inebilizumab MEDI-551 Humanized monoclonal antibody IgG2κ ADCC Antineoplastic Refractory DLBCL phase II 2016 Disease modifying systemic sclerosis, multiple sclerosis Neuromyelitis optica Intravenous CD19 Infliximab Remicade FDA 1998 EU 1999 Inflectra FDA 2016 EU 2013 Remsima EU 2013 Human-murine chimera …

Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.

Eukaryotic elongation factor 1A (eEF1A), the second most abundant intracellular protein, not only plays a key role in peptide elongation, but is also capable of numerous moonlighting functions. Within malignant cells, eEF1A is by no means a neutral bystander but instead actively participates in oncogenic transformations via a myriad of molecular pathways. Thus far, a broad range of small-molecule inhibitors have been identified, which, despite their structural diversity, suppress tumor growth by targeting eEF1A. Interestingly, just as eEF1A enables its oncogenic potential far beyond boosting p

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… Building on this mechanistic insight, the first potent metarrestin-based proteolysis-targeting chimera (PROTAC) has been disclosed in the literature, exhibiting the effective, dose-dependent degradation of eEF1A2 in multiple cancer cell lines [ 84 ]. …

A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals.

BACKGROUND: Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS: In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by

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… Chimeras were identified and removed using uchime3_denovo, and sequences with ≥98% similarity were aligned to the zOTUs via usearch_global. …

Структура и состав микробных сообществ в водной толще Южного залива Мексики и обнаружение предполагаемых микроорганизмов, деградирующих углеводороды.

В ходе этого исследования была проведена оценка сообщества бактериопланктонов и его связи с экологическими переменными, включая общую концентрацию нефтяных углеводородов (ТПГ), в районе шельфа Юкатан в Южном заливе Мексики. Анализ разнообразия бета на основе последовательности 16S rRNA показал различия в структуре общины бактериопланктона между участками отбора проб. ПЕРМАНОВА указала, что эти изменения могут быть связаны главным образом с глубокими изменениями (см.5 в адрес 180 m), концентрация растворенного кислорода (2.06 в адрес 5.93 мг L-1), и концентрация хлорофилла (0.184 в адрес 7.65 м

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… Chimeras were removed with the ‘consensus’ method. The representative ASVs were taxonomically assigned with the V‐SEARCH consensus taxonomy classifier plugin (Rognes et al., 2016 ) using the SILVA database (v.128) as a reference. …

Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.

P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and si

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… displaying potent reduction of leukocyte–endothelial interactions in vitro along with a commensurate decrease in inflammation and pancreatic injury in murine models of cerulein- and l -arginine–induced acute pancreatitis. 46 In the late 1990s, Wyeth Pharmaceuticals developed a recombinant immunoglobulin chimera …

Novel Short PEG Chain-Substituted Porphyrins: Synthesis, Photochemistry, and In Vitro Photodynamic Activity against Cancer Cells.

This work presents the synthesis and characterization of metal-free, zinc (II), and cobalt (II) porphyrins substituted with short PEG chains. The synthesized compounds were characterized by UV-Vis, 1H and 13C NMR spectroscopy, and MALDI-TOF mass spectrometry. The origin of the absorption bands for tested compounds in the UV-Vis range was determined using a computational model based on the electron density functional theory (DFT) and its time-dependent variant (TD-DFT). The photosensitizing activity was evaluated by measuring the ability to generate singlet oxygen (ΦΔ), which reached values up

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… A Revisit of High Collision Energy Effects on Collision-Induced Dissociation Spectra Using Matrix-Assisted Laser Desorption/Ionization Tandem Time-of-Flight Mass Spectrometry (MALDI-LIFT-TOF/TOF): Application to the Sequencing of RNA/DNA Chimeras Rapid Commun. …

Emerging Strategies Targeting Catabolic Muscle Stress Relief.

Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. Thi

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… Furthermore, PROteolysis TArgeting Chimeras (PROTACs) is a promising and appealing technology able to regulate protein function by degrading target proteins instead of inhibiting them. …

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

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… This “classical scaffold + targeted degradation” chimera could specifically induce complete tubulin degradation, fundamentally circumventing the systemic toxicity driven by high-dose or long-term traditional inhibition ( Assunçao et al., 2025 ). …

Strategies for p53 Activation and Targeted Inhibitors of the p53-Mdm2/MdmX Interaction.

p53 is a tumor suppressor gene and is regarded as one of the most crucial genes in protecting humans against cancer. The protein Mdm2 and its homolog MdmX serve as negative regulators of p53. In nearly half of cancer cells, there is an overexpression of Mdm2 and MdmX, which inhibit p53 activity. Furthermore, Mdm2's E3 ubiquitin ligase activity promotes the ubiquitination and degradation of p53. Therefore, blocking the interaction between p53 and Mdm2/MdmX to prevent the degradation of wild-type p53 is an effective strategy for inhibiting tumor growth. This paper primarily discusses the regulat

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… In recent years, strategies utilizing Proteolysis-targeting chimeras (PROTACs) to restore p53 activity have gained significant attention. …

Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular

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… Ribonuclease targeting chimeras (RiboTACs) are bifunctional molecules that can simultaneously bind to lncRNA and recruit ribonucleases to degrade specific lncRNAs, enabling the selective degradation of pathogenic lncRNAs [ 116 ]. …