Repurposing metabolic regulators: antidiabetic drugs as anticancer agents

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Sept. 28, 2024

Abstract Drug repurposing in cancer taps into the capabilities of existing drugs, initially designed for other ailments, as potential treatments. It offers several advantages over traditional drug discovery, including reduced costs, development timelines, and a lower risk adverse effects. However, not all classes align seamlessly with patient's condition or long-term usage. Hence, chronically used drugs presents more attractive option. On hand, metabolic reprogramming being an important hallmark paves regulators possible therapeutics. This review emphasizes importance current insights antidiabetic metformin, sulfonylureas, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase 4 (DPP-4) glucagon-like peptide-1 receptor agonists (GLP-1RAs), thiazolidinediones (TZD), α-glucosidase against various types cancers. Antidiabetic regulating pathways have gained considerable attention research. The literature reveals complex relationship between risk. Among metformin may possess anti-cancer properties, potentially reducing cell proliferation, inducing apoptosis, enhancing sensitivity to chemotherapy. revealed heterogeneous responses. Sulfonylureas TZDs demonstrated consistent activity, while SGLT2 inhibitors DPP-4 shown some benefits. GLP-1RAs raised concerns due associations increased certain highlights that further research is warranted elucidate mechanisms underlying effects these establish their efficacy safety clinical settings.

Language: Английский

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Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS

ACS Omega, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 10, 2024

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper lower motor neurons, resulting in debilitating muscle weakness atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges managing disease that affects approximately two individuals per 100,000 people annually. To address urgent need ALS treatments, we conducted drug repurposing study using combination bioinformatics tools molecular docking techniques. We analyzed sporadic ALS-related genes from GEO database identified key signaling pathways involved pathogenesis through pathway analysis DAVID. Subsequently, utilized Clue Connectivity Map to identify potential candidates performed AutoDock Vina evaluate binding affinity short-listed drugs genes. Our Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, Tolterodine as treatment. Notably, Lestaurtinib demonstrated high toward multiple proteins, suggesting its broad-spectrum therapeutic agent ALS. Additionally, revealed NOS3 gene interacts with all drugs, possible involvement mechanisms underlying these Overall, our provides systematic framework identifying therapy highlights promising strategy discovering new therapies diseases.

Language: Английский

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Architecting the metabolic reprogramming survival risk framework in LUAD through single-cell landscape analysis: three-stage ensemble learning with genetic algorithm optimization

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 15, 2024

Abstract Recent studies have increasingly revealed the connection between metabolic reprogramming and tumor progression. However, specific impact of on inter-patient heterogeneity prognosis in lung adenocarcinoma (LUAD) still requires further exploration. Here, we introduced a cellular hierarchy framework according to malignant gene set, named & metabolism (MMR), reanalyze 178,739 single-cell reference profiles. Furthermore, proposed three-stage ensemble learning pipeline, aided by genetic algorithm (GA), for survival prediction across 9 LUAD cohorts ( n = 2066). Throughout pipeline developing three stage-MMR (3 S-MMR) score, double training sets were implemented avoid over-fitting; gene-pairing method was utilized remove batch effect; GA harnessed pinpoint optimal basic learner combination. The novel 3 S-MMR score reflects various aspects biology, provides new insights into precision medicine patients, may serve as generalizable predictor immunotherapy response. To facilitate clinical adoption developed an easy-to-use web tool risk scoring well therapy stratification patients. In summary, validated model within reprogramming, offering potential treatment effective approach prognostic models other diseases.

Language: Английский

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The Vital Role Played by Deferiprone in the Transition of Thalassaemia from a Fatal to a Chronic Disease and Challenges in Its Repurposing for Use in Non-Iron-Loaded Diseases

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(7), P. 1016 - 1016

Published: July 18, 2023

The iron chelating orphan drug deferiprone (L1), discovered over 40 years ago, has been used daily by patients across the world at high doses (75–100 mg/kg) for more than 30 with no serious toxicity. level of safety and simple, inexpensive synthesis are some many unique properties L1, which played a major role in contribution transition thalassaemia from fatal to chronic disease. Other valuable clinical L1 relation pharmacology metabolism include: oral effectiveness, improved compliance compared prototype therapy subcutaneous deferoxamine; highly effective removal all iron-loaded organs, particularly heart, is target organ toxicity cause mortality thalassaemic patients; an ability achieve negative balance, completely remove excess iron, maintain normal stores rapid absorption stomach clearance body, allowing greater frequency repeated administration overall increased efficacy excretion, dependent on dose also concentration achieved site action; its cross blood–brain barrier treat malignant, neurological, microbial diseases affecting brain. Some differential pharmacological activity among generally shown absorption, distribution, metabolism, elimination, (ADMET) drug. Unique exhibited comparison other drugs include specific protein interactions antioxidant effects, such as transferrin lactoferrin; inhibition copper catalytic production free radicals, ferroptosis, cuproptosis; iron-containing proteins associated different pathological conditions. have attracted interest investigators repurposing use conditions, including cancer, neurodegenerative renal radical pathology, metal intoxication Fe, Cu, Al, Zn, Ga, In, U, Pu, diseases. Similarly, increase prospects wider optimizing therapeutic efforts fields medicine, synergies drugs.

Language: Английский

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Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 29, 2024

Abstract Background Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) variant syndrome (VS) exhibit a complex overlap of AIH features with PBC, leading to poorer prognoses than those PBC or alone. The biomarkers associated drug response potential molecular mechanisms in this have not been fully elucidated. Methods Whole-transcriptome sequencing was employed discern differentially expressed (DE) RNAs within good responders (GR) poor (PR) among patients PBC/AIH VS. Subsequent gene ontology (GO) analysis Kyoto Encyclopedia Genes Genomes (KEGG) pathway were conducted for the identified DE RNAs. Plasma metabolomics delineate metabolic profiles distinguishing PR GR groups. quantification immune cell cytokines achieved through flow cytometry immunoassay technology. Uni- multivariable logistic regression analyses construct predictive model insufficient biochemical response. performance assessed by computing area under receiver operating characteristic (AUC) curve, sensitivity, specificity. Findings 224 mRNAs, 189 long non-coding RNAs, 39 circular 63 microRNAs. Functional revealed enrichment lipid pathways Metabolomics disclosed dysregulated metabolism PC (18:2/18:2) (16:0/20:3) as predictors. CD4 + T helper (Th) cells, including Th2 cells regulatory (Tregs), upregulated group. Pro-inflammatory (IFN-γ, TNF-α, IL-9, IL-17) downregulated group, while anti-inflammatory (IL-10, IL-4, IL-5, IL-22) elevated. Regulatory networks constructed, identifying CACNA1H ACAA1 target genes. A based on these indicators demonstrated an AUC 0.986 primary cohort 0.940 validation predicting complete Conclusion combined integrating genomic, metabolic, cytokinomic high accuracy Early recognition individuals at elevated risk allows prompt initiation additional treatments.

Language: Английский

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Machine Learning Applications for Drug Repurposing

Published: June 19, 2024

Machine learning (ML) is revolutionizing drug repurposing, offering a more efficient, cost-effective approach to discovery by identifying new therapeutic uses for existing drugs. ML algorithms process large, complex biomedical datasets, find hidden patterns that reveal unexpected links between drugs and diseases, predict potential side effects. This advancement holds significant promise precision medicine personalized healthcare. chapter aims explore the growing role of in an emergent frontier identify drugs, thereby accelerating pace medical innovation while mitigating cost risk. The discusses various case studies, demonstrating application drug–disease connections predicting adverse reactions, significantly contributing medicine. In addition, investigates successes challenges encountered this nascent field, highlighting modernize discovery. Emphasis placed on ethical privacy concerns surrounding use patient data models, urging need robust regulations. comprehensive review serves as practical guide those at intersection pharmaceutical research, clinical practice, computer sciences, advocating synergetic these fields advancing

Language: Английский

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Integrated ML-Based Strategy Identifies Drug Repurposing for Idiopathic Pulmonary Fibrosis

ACS Omega, Journal Year: 2024, Volume and Issue: 9(27), P. 29870 - 29883

Published: June 27, 2024

Idiopathic pulmonary fibrosis (IPF) affects an estimated global population of around 3 million individuals. IPF is a medical condition with unknown cause characterized by the formation scar tissue in lungs, leading to progressive respiratory disease. Currently, there are only two FDA-approved small molecule drugs specifically for treatment and this has created demand rapid development treatment. Moreover, denovo drug time cost-intensive less than 10% success rate. Drug repurposing currently most feasible option rapidly making market rare sporadic Normally, begins screening using computational tools, which results low hit Here, integrated machine learning-based strategy developed significantly reduce false positive outcomes introducing predock machine-learning-based predictions followed literature GSEA-assisted validation pathway prediction. The deployed 1480 clinical trial screen them against "TGFB1", "TGFB2", "PDGFR-a", "SMAD-2/3", "FGF-2", more proteins resulting 247 total 27 potentially repurposable drugs. GSEA suggested that 72 (29.14%) have been tried IPF, 13 (5.2%) already used lung fibrosis, 20 (8%) tested other fibrotic conditions such as cystic renal fibrosis. Pathway prediction remaining 142 was carried out 118 distinct pathways. Furthermore, analysis revealed 29 pathways were directly or indirectly involved 11 involved. 15 potential combinations showing strong synergistic effect IPF. reported here will be useful developing treating related conditions.

Language: Английский

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De novo in silico screening of natural products for antidiabetic drug discovery: ADMET profiling, molecular docking, and molecular dynamics simulations

In Silico Pharmacology, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 17, 2025

Language: Английский

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A comprehensive review on coating techniques to suppress the dendrites issue and improve the performance of lithium-ion batteries

Journal of Coatings Technology and Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Language: Английский

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Mastalgia in Fibrocystic Changes; From the Diagnosis Bench to Innovative Therapy: A Narrative Review

The Open Medicinal Chemistry Journal, Journal Year: 2025, Volume and Issue: 19(1)

Published: April 16, 2025

Fibrocystic breast change (FBC) is a prevalent benign condition that affects women of reproductive age. Hormonal fluctuation during the menstrual cycle suggested pathology. Affected suffer cyclical pain (mastalgia), texture, and nipple discharge. Multiple diagnostic therapeutic approaches were used to address mastalgia in FCB; last decade witnessed considerable advancement modalities, showing variable degrees efficacy alleviating mastalgia. This review aims examine recent data linked FCB diagnosis, addition discussing comparing latest options cases. An online search was conducted via four major electronic databases using keywords related FCB, pathology, imaging, therapy. Data interest extracted analyzed. Our findings indicate mammography takes lead ultrasound complementary. Innovative bioinformatics holds promise improving precision outcomes. Lifestyle changes remain first option, which combined with drug therapy tailored according etiology nature varying degree efficacy. strategies discussed, good efficacy, low rate side effects, high patient acceptability. Empowering physicians knowledge will refine challenges, guide choices, enhance outcomes, allow holistically centered health care. Future research needed explore optimal follow-up approaches, added best treatment combinations newer therapies better safety profiles more satisfaction.

Language: Английский

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