ChemMedChem最新文献_第4页

Protonation effects in protein-ligand complexes - a case study of endothiapepsin and pepstatin A with computational and experimental methods. 蛋白质配体复合物中的质子化效应——以计算和实验方法研究内硫肽素和胃抑素a为例。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-13 DOI: 10.1002/cmdc.202400953

Paul Czodrowski, Helge Vatheuer, Oscar Palomino-Hernandez, Janis Müller, Phillip Galonska, Serghei Glinca

{"title":"Protonation effects in protein-ligand complexes - a case study of endothiapepsin and pepstatin A with computational and experimental methods.","authors":"Paul Czodrowski, Helge Vatheuer, Oscar Palomino-Hernandez, Janis Müller, Phillip Galonska, Serghei Glinca","doi":"10.1002/cmdc.202400953","DOIUrl":"https://doi.org/10.1002/cmdc.202400953","url":null,"abstract":"Protonation states serve as an essential molecular recognition motif for biological processes. Their correct consideration is key to successful drug design campaigns, since chemoinformatic tools usually deal with default protonation states of ligands and proteins and miss atypical protonation states. The protonation pattern for the Endothiapepsin/PepstatinA (EP/pepA) complex is investigated using different dry lab and wet lab techniques. ITC experiments revealed an uptake of more than one mole of protons upon pepA binding to EP. Since these experiments were performed at physiological conditions (and not at pH=4 at which a large variety of crystal structures is available), a novel crystal structure at pH=7.6 was determined. This crystal structure showed that only modest structural changes occur upon increasing the pH value. This lead to computational studies (Poisson Boltzmann calculations and constant pH MD simulations) to reveal the exact location of the protonation event. Both computational studies could reveal a significant pKa shift resulting in non-default protonation state and that the catalytic dyad is responsible for the uptake of protons. This study shows that assessing protonation states for two separate systems (protein and ligand) might result in the incorrect assignment of protonation states and hence incorrect calculation of binding energy.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400953"},"PeriodicalIF":3.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus. 逆转谷黄肠球菌氨基糖苷耐药的APH抑制剂。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-13 DOI: 10.1002/cmdc.202400842

Elise Kaplan, Laurent Chaloin, Jean-François Guichou, Kévin Berrou, Rahila Rahimova, Gilles Labesse, Corinne Lionne

{"title":"APH Inhibitors that Reverse Aminoglycoside Resistance in Enterococcus casseliflavus.","authors":"Elise Kaplan, Laurent Chaloin, Jean-François Guichou, Kévin Berrou, Rahila Rahimova, Gilles Labesse, Corinne Lionne","doi":"10.1002/cmdc.202400842","DOIUrl":"10.1002/cmdc.202400842","url":null,"abstract":"Aminoglycoside-phosphotransferases (APHs) are a class of bacterial enzymes that mediate acquired resistance to aminoglycoside antibiotics. Here we report the identification of small molecules counteracting aminoglycoside resistance in Enterococcus casseliflavus. Molecular dynamics simulations were performed to identify an allosteric pocket in three APH enzymes belonging to 3' and 2'' subfamilies in which we then screened, in silico, 12,000 small molecules. From a subset of only 14 high-scored molecules tested in vitro, we identified a compound, named here EK3, able to non-competitively inhibit the APH(2'')-IVa, an enzyme mediating clinical gentamicin resistance. Structure-activity relationship (SAR) exploration of this hit compound allowed us to identify a molecule with improved enzymatic inhibition. By measuring bacterial sensitivity, we found that the three best compounds in this series restored bactericidal activity of various aminoglycosides, including gentamicin, without exhibiting toxicity to HeLa cells. This work not only provides a basis to fight aminoglycoside resistance but also highlights a proof-of-concept for the search of allosteric modulators by using in silico methods.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400842"},"PeriodicalIF":3.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Green Light Activated Dual-Action Pt(IV) Prodrug With Enhanced PDT activity. 具有增强PDT活性的绿光激活双作用Pt（IV）前药。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-10 DOI: 10.1002/cmdc.202400786

Olga O Krasnovskaya, Daniil Spector, Vladislav Bykusov, Yulia Isaeva, Yuri Grishin, Roman Akasov, Anastasia Zharova, Igor Rodin, Vladimir Kuzmin, Mikhail Vokuev, Vita Nikitina, Alexander Martynov, Elena Beloglazkina

{"title":"Green Light Activated Dual-Action Pt(IV) Prodrug With Enhanced PDT activity.","authors":"Olga O Krasnovskaya, Daniil Spector, Vladislav Bykusov, Yulia Isaeva, Yuri Grishin, Roman Akasov, Anastasia Zharova, Igor Rodin, Vladimir Kuzmin, Mikhail Vokuev, Vita Nikitina, Alexander Martynov, Elena Beloglazkina","doi":"10.1002/cmdc.202400786","DOIUrl":"https://doi.org/10.1002/cmdc.202400786","url":null,"abstract":"Light induced release of cisplatin from Pt(IV) prodrugs is a promising tool for precise spatiotemporal control over the antiproliferative activity of Pt-based chemotherapeutic drugs. A combination of light-controlled chemotherapy (PACT) and photodynamic therapy (PDT) in one molecule has the potential to overcome crucial drawbacks of both Pt-based chemotherapy and PDT via a synergetic effect. Herein we report green-light-activated Pt(IV) prodrug GreenPt with BODIPY-based photosentitizer in the axial position with an incredible high light response and singlet oxygen generation ability. GreenPt demonstrated the ability to release cisplatin under low-dose green light irradiation up to 1 J/cm2. The investigation of the photoreduction mechanism of GreenPt prodrug using DFT modeling and ΔG0 PET estimation revealed that the anion-radical formation and substituent photoinduced electron transfer from the triplet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin. Green-light-activated BODIPY-based photosentitizers 5 and 8 demonstrated outstanding photosensitizing properties with an extraordinary phototoxicity index (PI) >1300. GreenPt prodrug demonstrated gradual intracellular accumulation and light-induced phototoxicity with PI > 100, thus demonstrating dual action through light-controlled release of both cisplatin and a potent BODIPY-based photosensitizer.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400786"},"PeriodicalIF":3.6,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Harnessing the Sulfur-for-Oxygen Shift: A Magic Bullet for Dynamic Photophysical and Anticancer Activities of Indole-Barbituric Acid Construct. 利用硫-氧转换：吲哚-巴比妥酸结构的动态光物理和抗癌活性的灵丹妙药。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-09 DOI: 10.1002/cmdc.202400849

Kartikay Tyagi, Reena Kumari, V Venkatesh

{"title":"Harnessing the Sulfur-for-Oxygen Shift: A Magic Bullet for Dynamic Photophysical and Anticancer Activities of Indole-Barbituric Acid Construct.","authors":"Kartikay Tyagi, Reena Kumari, V Venkatesh","doi":"10.1002/cmdc.202400849","DOIUrl":"10.1002/cmdc.202400849","url":null,"abstract":"The development of small molecule-based drugs emerged as a cornerstone of modern drug discovery. Structural activity relationship (SAR) studies in medicinal chemistry are crucial for lead optimization, where a subtle change in the substituent can significantly alter its binding affinity with the biological target. Herein, a highly efficient single-atom substitution (SAS) approach has been developed, where sulfur for oxygen strategy is utilized as a powerful molecular editing technique to identify N-vinyl Indole-thiobarbituric acid (6 a) as a novel small molecule-based scaffold with tunable photophysical and antiproliferative activities. A series of NIR-emitting indole-barbituric/thiobarbituric acid conjugates exhibiting aggregation-induced emission (AIE) were prepared, where the replacement of oxygen for sulfur strategy emerged as a magic bullet. On the evaluation of photophysical properties and chemopreventive efficacies, a significant improvement in the absorption and emission profile, cellular uptake, and antiproliferative activity was noted for sulfur counterparts. From the pool of the molecules, the lead molecule 6 a unveils a 55 nm emission shift, 142-fold increased anticancer profile, and ~4-fold elevated cellular uptake. Furthermore, the colocalization experiment unravels the nuclear localization of 6 a, where it causes severe DNA damage, arrests the cell cycle in the G2/M phase, and leads to the activation of p53-mediated apoptosis. Our experimental findings represent 6 a as a potential lead molecule possessing excellent anticancer potency in the HCT 116 cell line and HCT 116-derived 3D spheroid model.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400849"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Improving Affinity while Reducing Kidney Uptake of CXCR4-Targeting Radioligands Derived from the Endogenous Antagonist EPI-X4. 内源性拮抗剂EPI-X4衍生的靶向cxcr4的放射配体在提高亲和力的同时减少肾脏摄取。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-09 DOI: 10.1002/cmdc.202400773

Raghuvir H Gaonkar, Thibaud Bailly, Jacopo Millul, Rosalba Mansi, Mirja Harms, Jan Münch, Melpomeni Fani

{"title":"Improving Affinity while Reducing Kidney Uptake of CXCR4-Targeting Radioligands Derived from the Endogenous Antagonist EPI-X4.","authors":"Raghuvir H Gaonkar, Thibaud Bailly, Jacopo Millul, Rosalba Mansi, Mirja Harms, Jan Münch, Melpomeni Fani","doi":"10.1002/cmdc.202400773","DOIUrl":"10.1002/cmdc.202400773","url":null,"abstract":"The C-X-C chemokine receptor 4 (CXCR4) is highly upregulated in most cancers, making it an ideal target for delivering radiation therapy to tumors. We previously demonstrated the feasibility of targeting CXCR4 in vivo using a radiolabeled derivative of EPI-X4, an endogenous CXCR4 antagonist, named DOTA-K-JM#173. However, this derivative showed undesirable accumulation in the kidneys, which would limit its clinical use. In this study, we identified that removing a positive charge from the peptide sequence significantly reduced renal uptake. We evaluated a series of optimized derivatives lacking this positive charge, in vitro and in vivo in a xenografted athymic nude mice model, after radiolabeling with 177Lu. The most promising derivatives were further assessed in vivo after 68Ga labeling. Among them, we identified DOTA-JM#173 and D-L1-DOTA-JM#173, where the D-Ile1 was replaced by D-Leu1, two optimized derivatives with a lysine residue removed. These two molecules represent the most advanced DOTA-conjugated ligands derived from EPI-X4 for CXCR4-directed theranostic applications, offering enhanced potential for targeted cancer treatment.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400773"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New Hydrazone Derivatives Based on Pyrazolopyridothiazine Core as Cytotoxic Agents to Colon Cancers: Design, Synthesis, Biological Evaluation, and Molecular Modeling. 基于吡唑吡嗪核心的新型腙衍生物作为结肠癌细胞毒性药物：设计、合成、生物学评价和分子模型。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-09 DOI: 10.1002/cmdc.202400687

Teresa Glomb, Kamila Środa-Pomianek, Anna Palko-Łabuz, Olga Wesołowska, Agnieszka Wikiera, Kamil Wojtkowiak, Aneta Jezierska, Andrzej Kochel, Roman Lesyk, Piotr Świątek

{"title":"New Hydrazone Derivatives Based on Pyrazolopyridothiazine Core as Cytotoxic Agents to Colon Cancers: Design, Synthesis, Biological Evaluation, and Molecular Modeling.","authors":"Teresa Glomb, Kamila Środa-Pomianek, Anna Palko-Łabuz, Olga Wesołowska, Agnieszka Wikiera, Kamil Wojtkowiak, Aneta Jezierska, Andrzej Kochel, Roman Lesyk, Piotr Świątek","doi":"10.1002/cmdc.202400687","DOIUrl":"10.1002/cmdc.202400687","url":null,"abstract":"In this research, a series of novel hydrazone derivatives based on pyrazolopyridothiazinylacetohydrazide were designed, synthesized, and evaluated for their in vitro cytotoxic potency on several human colon cancer cells (HTC116, HT-29, and LoVo). After MTT and SRB assays four of the most active derivatives: hydrazide GH and hydrazones GH7, GH8, and GH11, were chosen for further investigation. Hydrazone GH11 had the highest cytotoxic activity (IC50 values of c.a. 0.5 μM). Additionally, the impact of novel derivatives on the oxidative stress level, apoptosis induction, and modulation of inflammation in colon cancer cells was examined. In all studies, the activity of the derivatives increased in order GH < GH7 < GH8 < GH11. At the same time, most of the research was conducted on compounds combined with apple pectin (PC). The most interesting observation was that all the studied derivatives applied together with PC showed significantly higher activity than observed in the case of using PC, hydrazide, or hydrazones separately. Finally, computational chemistry methods (molecular modeling and Density Functional Theory - DFT) were used to complement the experimental studies.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400687"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seeing in the Future - a Perspective on Combining Light with Chemical Biology Approaches to Treat Retinal Pathologies. 展望未来——光与化学生物学结合治疗视网膜病变的展望。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-08 DOI: 10.1002/cmdc.202400827

Alexandre Specht, Maxime Klimezak, Sidney Cambridge

{"title":"Seeing in the Future - a Perspective on Combining Light with Chemical Biology Approaches to Treat Retinal Pathologies.","authors":"Alexandre Specht, Maxime Klimezak, Sidney Cambridge","doi":"10.1002/cmdc.202400827","DOIUrl":"https://doi.org/10.1002/cmdc.202400827","url":null,"abstract":"New concepts to treat eye diseases have emerged that elegantly combine unnatural light exposure with chemical biology approaches to achieve superior cellular specificity and, as a result, improvement of visual function. Historically, light exposure without further molecular eye treatment has offered limited success including photocoagulation to halt pathological blood vessel growth or low light exposure to stimulate retinal cell viability. To add cellular specificity to such treatments, researchers have introduced various biological or chemical light-sensing molecules and combined those with light exposure. (Pre-)clinical trials describe the use of optogenetics and channelrhodpsins, i. e. light-sensitive ion channels, in patient vision restoration. In the chemical arena, pharmacological agents, rendered light-sensitive by reversible modification with photosensitive protecting compounds (\"caging\"), have been applied to eyes of living mice to photo-release specific cellular activities. Among these were successful proof-of-principle experiments that were conducted to establish photo-sensitive gene therapies in the eye. For light-mediated treatment in combination with chemical biology, we wish to describe here the current frontiers of research in vision restoration with an eye on differences between biological and chemical light-sensing molecules, patient requirements, and future outlooks.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400827"},"PeriodicalIF":3.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of a Gemcitabine Prodrug and its Encapsulation into Polymeric Nanoparticles for Improved Therapeutic Efficacy. 吉西他滨前药的合成及其聚合纳米颗粒的包封研究。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-07 DOI: 10.1002/cmdc.202400532

Kajal Kaliya, Neha Bhardwaj, Ruchika, Ankit Saneja

{"title":"Synthesis of a Gemcitabine Prodrug and its Encapsulation into Polymeric Nanoparticles for Improved Therapeutic Efficacy.","authors":"Kajal Kaliya, Neha Bhardwaj, Ruchika, Ankit Saneja","doi":"10.1002/cmdc.202400532","DOIUrl":"10.1002/cmdc.202400532","url":null,"abstract":"Gemcitabine (GEM), a chemotherapeutic agent, is widely used to treat various neoplastic conditions, such as pancreatic, lung, breast, and ovarian cancer. However, its therapeutic effectiveness is often hindered by its short half-life and susceptibility to enzymatic degradation. To address these limitations, in this research, five new conjugates of GEM were synthesized by conjugating its N-4 amino group with five different acids [4-decenoic acid (4Dec), lipoic acid (Lipo), lauric acid (Laur), 5-benzyl N-(tert-butoxycarbonyl)- L-glutamate (Glu), and decanoic acid (Dec)]. The anticancer potential of these conjugates was evaluated using CCK-8 assay. Among the synthesized conjugates, 4Dec-GEM demonstrated comparable cytotoxic activity to native GEM. The mechanistic insight of 4Dec-GEM was investigated using annexin-V FITC/propidium iodide staining, reactive oxygen species generation, and mitochondrial membrane potential loss assays. To further enhance its therapeutic efficacy, 4Dec-GEM was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles using single-emulsion method using high-pressure homogenization. The developed nanoparticles were characterized by various techniques (TEM, FT-IR, DSC, p-XRD) and demonstrated successful entrapment of 4Dec-GEM inside PLGA nanoparticles. Finally, the cytotoxicity of developed nanoparticles demonstrated improved anticancer activity as compared to native GEM in cancerous cell lines. Our study demonstrated that the combination of prodrug and nanoparticle approach can be a promising approach to augment the therapeutic efficacy of GEM.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400532"},"PeriodicalIF":3.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CORRIGENDUM: α-Triazolylboronic Acids: A Novel Scaffold to Target FLT3 in AML. 更正：α-三唑基硼酸：AML中靶向FLT3的新型支架。

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-06 DOI: 10.1002/cmdc.202400982

引用次数: 0

Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we? 在toll样受体之外。结构依赖性脂多糖识别系统：我们走了多远？

IF 3.6 4区医学

ChemMedChem Pub Date : 2025-01-03 DOI: 10.1002/cmdc.202400780

Stefania De Chiara, Luca De Simone Carone, Roberta Cirella, Emanuela Andretta, Alba Silipo, Antonio Molinaro, Marcello Mercogliano, Flaviana Di Lorenzo

{"title":"Beyond the Toll-Like Receptor 4. Structure-Dependent Lipopolysaccharide Recognition Systems: How far are we?","authors":"Stefania De Chiara, Luca De Simone Carone, Roberta Cirella, Emanuela Andretta, Alba Silipo, Antonio Molinaro, Marcello Mercogliano, Flaviana Di Lorenzo","doi":"10.1002/cmdc.202400780","DOIUrl":"10.1002/cmdc.202400780","url":null,"abstract":"With an enormous potential in immunology and vaccinology, lipopolysaccharides (LPSs) are among the most extensively studied bacteria-derived molecules. LPS centered studies are countless, and their results reverberate in all areas of the life sciences, including chemistry, biology, genetics, biophysics, and medicine. Most of these research activities are focused on the LPS-induced immune response activation by means of Myeloid Differentiation protein-2/Toll Like Receptor 4 (MD-2/TLR4) complex, which currently is the most largely explored LPS sensing pathway. However, the enormous structural variability of LPS allows interactions with numerous other receptors involved in a wide range of equally important immunological scenarios. In this review, we explore these additional LPS recognition systems, which operate within interconnected signaling cascades, highlighting their role in maintaining physiological homeostasis and their involvement in the development of severe human diseases. Understanding these pathways, their interconnections, and the crosstalk between them and TLR4/MD-2 is essential for guiding the development of pharmacologically active molecules that could specifically modulate the inflammatory response, paving the way to new strategies for combating immune-mediated diseases and resistant infections.","PeriodicalId":147,"journal":{"name":"ChemMedChem","volume":" ","pages":"e202400780"},"PeriodicalIF":3.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0