Pharmacological research最新文献

{"title":"Properties of FDA-approved small molecule protein kinase inhibitors: A 2025 update","authors":"Robert Roskoski Jr.","doi":"10.1016/j.phrs.2025.107723","DOIUrl":"10.1016/j.phrs.2025.107723","url":null,"abstract":"<div><div>Because of the deregulation of protein kinase action in many inflammatory diseases and cancer, the protein kinase family has become one of the most significant drug targets in the 21st century. There are 85 FDA-approved protein kinase antagonists that target about two dozen different enzymes and four of these drugs were approved in 2024 and a fifth was approved in 2025. Of these drugs, five target dual specificity protein kinases (MEK1/2), fourteen inhibit protein-serine/threonine protein kinases, twenty-one block nonreceptor protein-tyrosine kinases, and 45 target receptor protein-tyrosine kinases. The data indicate that 75 of these drugs are prescribed for the treatment of neoplasms. Seven drugs (abrocitinib, baricitinib, deucravacitinib, deuruxolitinib, ritlecitinib, tofacitinib, upadacitinib) are prescribed for the management of inflammatory diseases (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, and ulcerative colitis). Of the 85 FDA-approved agents, about two dozen are used in the treatment of multiple diseases. The following four drugs received FDA approval in 2024 – deuruxolitinib (alopecia areata), ensartinib and lazertinib (non-small cell lung cancer), and tovorafenib (pediatric glioma) while mirdametinib was approved in 2025 for the treatment of type I neurofibromatosis (von Recklinghausen disease). Apart from netarsudil, temsirolimus, and trilaciclib, the approved protein kinase blockers are orally bioavailable. This article summarizes the physicochemical properties of all 85 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 39 of the 85 FDA-approved drugs have a least one Lipinski rule of 5 violation.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107723"},"PeriodicalIF":9.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin3 attenuates pressure overload-induced pathological myocardial remodeling by inhibiting cardiomyocyte cuproptosis","authors":"Binghui Kong ,&nbsp;Xuehui Zheng ,&nbsp;Yang Hu ,&nbsp;Yuan Zhao ,&nbsp;Jinghan Hai ,&nbsp;Yun Ti ,&nbsp;Peili Bu","doi":"10.1016/j.phrs.2025.107739","DOIUrl":"10.1016/j.phrs.2025.107739","url":null,"abstract":"<div><div>Pathological myocardial remodelling is the initiation of pressure overload-induced heart failure, and its involvement in the associated molecular mechanisms remains to be fully elucidated. The aim of this study was to investigate whether Sirtuin3 (SIRT3) can affect pathological myocardial remodeling by regulating cellular cuproptosis and its potential mechanisms. In this study, we found that pressure overload induced pathologic myocardial remodeling in which cardiomyocytes showed a distinct cuproptosis signature accompanied by downregulation of SIRT3 expression. In vitro experiments demonstrated that copper ions reduced SIRT3 expression by 40 % (p &lt; 0.01) via lysosomal degradation. In vivo validation showed that pressure overload reduced SIRT3 expression by 35 % (p &lt; 0.01) in myocardial tissue. And SIRT3 knockdown increased pressure overload-induced pathological myocardial remodeling and cardiomyocyte cuproptosis. In contrast, cardiomyocytes-specific overexpression of SIRT3 by adeno-associated virus vectors attenuated pressure overload-induced pathologic myocardial remodeling and was unaffected by circulating levels of copper ions and hepatic and renal impairment. Mechanistically, the reduction of SIRT3 induced cardiomyocytes to become copper ion-sensitive state cells by affecting the binding of copper ion transporter proteins to microtubule-associated protein 1 light chain 3 beta(LC3B) in cardiomyocytes. Disturbance of copper ion homeostasis in cardiomyocytes leads to accumulation of copper ions in cardiomyocytes and the development of cuproptosis. These findings elucidate a novel mechanism by which SIRT3 affects cardiomyocyte death in pressure overload-induced pathologic myocardial remodeling and suggest the great potential of SIRT3-regulated cuproptosis of cardiomyocytes in the prevention or treatment of pathologic myocardial remodeling.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107739"},"PeriodicalIF":9.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTPRG-AS1 regulates the KITLG/KIT pathway through the ceRNA axis to promote the malignant progression of gastric cancer and the intervention effect of Compound Kushen injection on it","authors":"Chao Wu ,&nbsp;Yifei Gao ,&nbsp;Zhengsen Jin ,&nbsp;Zhihong Huang ,&nbsp;Haojia Wang ,&nbsp;Shan Lu ,&nbsp;Siyu Guo ,&nbsp;Fanqin Zhang ,&nbsp;Jingyuan Zhang ,&nbsp;Jiaqi Huang ,&nbsp;Xiaoyu Tao ,&nbsp;Xinkui Liu ,&nbsp;Xiaomeng Zhang ,&nbsp;Leiming You ,&nbsp;Qinglin Li ,&nbsp;Jiarui Wu","doi":"10.1016/j.phrs.2025.107743","DOIUrl":"10.1016/j.phrs.2025.107743","url":null,"abstract":"<div><div>Gastric cancer (GC) is a common malignant tumor with high mortality, recurrence, and metastasis rates. Compound Kushen injection (CKI) combination chemotherapy has been clinically used for the treatment of GC in China for many years, but its underlying mechanisms of action remain unclear. Recent reports have highlighted the important role of the competing endogenous RNA (ceRNA) mechanism of noncoding RNA (ncRNA) and messenger RNA (mRNA) formation in GC and other tumors. This study aimed to investigate the effects of CKI on GC from the ceRNA perspective. We confirmed the inhibitory effect of CKI on GC in mouse models and cell lines. By examining the GC cell lines sensitive to CKI treatment, we developed the CNScore method to analyze the ceRNA network, revealing that the CKI-GC ceRNA network promotes GC proliferation and metastasis through the PTPRG-AS1/hsa-miR-421/KITLG axis. Finally, we constructed GC cell models with PTPRG-AS1 overexpression or knockdown and GC liver metastasis models and found that PTPRG-AS1 can sponge hsa-miR-421, releasing KITLG and promoting GC proliferation and metastasis through the KITLG/KIT pathway. Taken together, CKI can suppress these malignant phenotypes by regulating the PTPRG-AS1/hsa-miR-421/KITLG axis.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107743"},"PeriodicalIF":9.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotropic role of mGluR7/MAPK signaling in the protection of intelectin-1 against cerebral ischemia-reperfusion injury","authors":"Xiaochen Niu ,&nbsp;Bodong Wang ,&nbsp;Aizhen Zhao ,&nbsp;Wenwen Yang ,&nbsp;Ning Li ,&nbsp;Wenzhen Shi ,&nbsp;Wangrui Lei ,&nbsp;Ying Cheng ,&nbsp;Baoying Wang ,&nbsp;Yang Yang ,&nbsp;Songdi Wu ,&nbsp;Ye Tian","doi":"10.1016/j.phrs.2025.107735","DOIUrl":"10.1016/j.phrs.2025.107735","url":null,"abstract":"<div><div>Acute ischemic stroke (AIS) is a serious neurological condition with limited treatment options available. Studies have shown that levels of the protein intelectin-1 (ITLN-1) are linked to stroke severity and poor neurological outcomes. This study aimed to evaluate the role and molecular mechanisms of ITLN-1 in AIS. This study found that ITLN-1 is widely expressed in various brain regions, while ITLN-1 levels were significantly decreased in the blood and brain tissues of ischemic stroke patients. ITLN-1 overexpression reduced neuronal damage and motor deficits in transient middle cerebral artery occlusion/reperfusion (tMCAO/R) treated mice. Treatment with Rh-omentin or ITLN-1 overexpression also had a protective effect in cellular injury models. RNA-seq analysis revealed that ITLN-1 impacts specific genes and pathways, particularly those related to mGluR7. Molecular docking and CO-IP analysis confirmed that ITLN-1 directly binds to and interacts with mGluR7. The study also showed that the ITLN-1/mGluR7 axis regulates MAPK cascades (ERK and p38) to reduce cerebral oxidative stress, mitochondrial dysfunction, and cell death. Additionally, the compound AKR-501 was found to have a protective effect against cerebral ischemia by modulating the ITLN-1/mGluR7/MAPK cascades. Overall, these findings suggest that targeting ITLN-1 could be a promising therapeutic approach for managing AIS, with important clinical implications.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107735"},"PeriodicalIF":9.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Intensity Statins Promote PCSK9 Secretion and aortic valve calcification in patients with severe aortic stenosis: In vitro and clinical evidence","authors":"Veronika A. Myasoedova ,&nbsp;Matteo Franchi ,&nbsp;Donato De Giorgi ,&nbsp;Alice Bonomi ,&nbsp;Vincenza Valerio ,&nbsp;Sergio Pirola ,&nbsp;Niccolò Andreani ,&nbsp;Valentina Rusconi ,&nbsp;Francesca Bertolini ,&nbsp;Ilaria Massaiu ,&nbsp;Gianluca Pontone ,&nbsp;Paolo Poggio","doi":"10.1016/j.phrs.2025.107737","DOIUrl":"10.1016/j.phrs.2025.107737","url":null,"abstract":"<div><div>Aortic stenosis (AS) is the most common valvular disease, characterized by progressive fibro-calcific remodeling of the aortic leaflets, leading to increased morbidity and mortality. It is now well known that statins influence the production of proprotein convertase subtilisin/kexin type 9 (PCSK9), which in turn is linked to calcification. Here, we found that statins significantly increased, in a dose dependent manner, both PCSK9 secretion and valve interstitial cell (VIC) calcification, <em>in vitro</em>. These effects were blunted by PCSK9 genetic knock-down or by PCSK9 antibody neutralization. In AS patients, contrast-enhanced computed tomography evaluation showed a higher aortic valve calcium (AVC) content in patients on high-intensity statins compared to low-intensity ones, with no significant difference between low-intensity statin and non-users. At follow-up, high-intensity statin users exhibited a higher annual AVC accumulation compared to low-intensity statins and non-users. In a real-world scenario, high-intensity statin therapy was associated with a 30 % increased rate of hospitalization for non-rheumatic aortic valve disease. Our findings highlight the need for further investigation into the intricate relationship between statin therapy and aortic valve health to identify the optimal lipid-lowering strategy in the management of patients at risk of developing or afflicted by AS.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107737"},"PeriodicalIF":9.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific effects of exogenous asparagine on colorectal tumor growth, 17β-estradiol levels, and aromatase","authors":"Oladimeji Aladelokun ,&nbsp;Katherine Benitez ,&nbsp;Yuying Wang ,&nbsp;Abhishek Jain ,&nbsp;Domenica Berardi ,&nbsp;Georgio Maroun ,&nbsp;Xinyi Shen ,&nbsp;Jatin Roper ,&nbsp;Joanna Gibson ,&nbsp;Kaelyn Sumigray ,&nbsp;Sajid A. Khan ,&nbsp;Caroline H. Johnson","doi":"10.1016/j.phrs.2025.107736","DOIUrl":"10.1016/j.phrs.2025.107736","url":null,"abstract":"<div><div>Sex-related differences in asparagine metabolism are associated with cancer prognosis. However, the effect of exogenous asparagine on colorectal cancer (CRC) growth in men and women remains unclear. This study aims to understand the relationship between exogenous asparagine supplementation and 17β-estradiol levels and to elucidate mechanisms underlying sex-dependent signaling during CRC development. We administered asparagine intraperitoneally to tumor-bearing male and female immunodeficient Rag2/Il2RG (R2G2) mice. Asparagine supplementation caused a significant increase in tumor asparagine levels in both the tumor-bearing male and female R2G2 mice but increased serum estradiol levels and suppressed tumor growth in female R2G2 mice only. Additionally, we combined transcriptome, metabolome, and immunochemical analyses, and found that intraperitoneal asparagine treatment induced sex-dependent intra-tumoral metabolic changes to asparagine, aspartate, glutamine and glutamate levels. We observed that in females, exogenous asparagine exerts a negative feed-back effect on <em>de novo</em> asparagine synthesis and is associated with the activation of a sub-population of macrophages that may secrete 17β-estradiol via an aromatase or cytochrome P450 family 19 (CYP19)-dependent mechanism. Conversely, in male mice, asparagine treatment augments tumor growth, and is related to decreased numbers of macrophages, and a reduction in CYP19-mediated 17β-estradiol secretion . Overall, our results reveal a novel and sex-specific role for exogenous asparagine during cancer progression and underscores the importance of understanding mechanisms that control asparagine biosynthesis.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107736"},"PeriodicalIF":9.1,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac PDK4 promotes neutrophilic PFKL methylation and drives the innate immune response in diabetic myocardial infarction","authors":"Song Yang ,&nbsp;Longxin Yan ,&nbsp;Lang Chen ,&nbsp;Gaijuan Su ,&nbsp;Long Yang ,&nbsp;Lili Gong ,&nbsp;Lihong Liu","doi":"10.1016/j.phrs.2025.107731","DOIUrl":"10.1016/j.phrs.2025.107731","url":null,"abstract":"<div><div>NETosis plays a pivotal role in the innate immune response after diabetic myocardial infarction (MI), exerting a profound influence on the overall pathological process and potential recovery outcomes. The metabolism of diabetic cardiomyocyte actively creates a specialized micro environment for the innate immune response after MI. However, the mechanism by which cardiac metabolism drives NETosis remains unclear. Utilizing public databases of human MI sc-RNA datasets, we discovered that cardiomyocyte PDK4 expression mediates the intensification of glycolysis, which is strongly correlated with NETosis. Through mass spectrometry imaging and phenotype assessment, we ascertained that specific knockout of PDK4 in cardiomyocytes (PDK4^fl/flMyh6^Cre, male, 6 weeks) led to a reduction in NETosis by restraining micro environmental lactate (LA) production. In addition, the role of LA in promoting NETosis has been further corroborated by <em>in vivo</em>/<em>in vitro</em> experiments involving LA supplementation and its absence. Moreover, LA redirects neutrophil metabolic flux from glycolysis to the pentose-phosphate pathway (PPP). Mechanistically, LA triggers metabolic remodeling through the PRMT9-mediated methylation of PFKL at the R301 residue, resulting in PFKL inactivation and the consequent restriction of glycolysis. Our findings reveal the crucial role of cardiomyocyte metabolism in NETosis, shedding light on the role of LA as a vital signaling molecule in the crosstalk between cardiomyocytes and neutrophils. Importantly, we screened pitavastatin, a potential inhibitor of PDK4 among the FDA-approved drugs, and verified that it can alleviate NETosis in diabetic MI, which provides a rationale for drug selection in diabetic MI patients.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107731"},"PeriodicalIF":9.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of semaphorin 3A in the pathogenesis and progression of Alzheimer’s disease and other aging-related diseases: A comprehensive review","authors":"Jiayu Yuan ,&nbsp;Rui Huang ,&nbsp;Jianfei Nao ,&nbsp;Xiaoyu Dong","doi":"10.1016/j.phrs.2025.107732","DOIUrl":"10.1016/j.phrs.2025.107732","url":null,"abstract":"<div><div>Aging serves as a pivotal factor in the etiology of numerous diseases, such as Alzheimer's disease (AD), Parkinson's disease, diabetes, osteoarthritis, atherosclerosis and aging-related macular degeneration. Notably, these diseases often interact with AD through various pathways, facilitating the onset or progression of one another. Semaphorin 3 A (Sema3A), a protein that is essential for axonal guidance during neural development, has recently been identified as a novel regulator in the pathogenesis and progression of multiple aging-related diseases. This article provides a comprehensive review of the expression patterns and mechanisms of action of Sema3A in these diseases. Specifically, Sema3A influences the occurrence and development of aging-related diseases by participating in oxidative stress, inflammatory responses, apoptosis, and synaptic plasticity. Therefore, therapeutic strategies targeting Sema3A present promising avenues for delaying the progression of aging-related diseases and offer novel insights and strategies for their treatment.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107732"},"PeriodicalIF":9.1,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in central-peripheral interaction organ crosstalk: the future of drug discovery and clinical trials","authors":"Yufeng Chen ,&nbsp;Mingrui Yang ,&nbsp;Qian Hua","doi":"10.1016/j.phrs.2025.107734","DOIUrl":"10.1016/j.phrs.2025.107734","url":null,"abstract":"<div><div>Drug discovery before the 20th century often focused on single genes, molecules, cells, or organs, failing to capture the complexity of biological systems. The emergence of protein-protein interaction network studies in 2001 marked a turning point and promoted a holistic approach that considers the human body as an interconnected system. This is particularly evident in the study of bidirectional interactions between the central nervous system (CNS) and peripheral organs, which are critical for understanding health and disease. Understanding these complex interactions requires integrating multi-scale, heterogeneous data from molecular to organ levels, encompassing both omics (e.g., genomics, proteomics, microbiomics) and non-omics data (e.g., imaging, clinical phenotypes). Artificial intelligence (AI), particularly multi-modal models, has demonstrated significant potential in analyzing CNS-peripheral organ interactions by processing vast, heterogeneous datasets. Specifically, AI facilitates the identification of biomarkers, prediction of therapeutic targets, and simulation of drug effects on multi-organ systems, thereby paving the way for novel therapeutic strategies. This review highlights AI's transformative role in CNS-peripheral interaction research, focusing on its applications in unraveling disease mechanisms, discovering drug targets, and optimizing clinical trials through patient stratification and adaptive trial design.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107734"},"PeriodicalIF":9.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multidisciplinary consensus on the diagnosis and management of patients with atypical Hemolytic Uremic Syndrome (complement-mediated TMA): Recommendations from Italian scientific societies, patient associations and regulators","authors":"Emma Diletta Stea ,&nbsp;Mariateresa Pugliano ,&nbsp;Roberta Gualtierotti ,&nbsp;Monica Mazzucato ,&nbsp;Luisa Santangelo ,&nbsp;Giuseppina Annicchiarico ,&nbsp;Alfredo Berardelli ,&nbsp;Stefano Bianchi ,&nbsp;Laura Bogliolo ,&nbsp;Paolo Chiandotto ,&nbsp;Giuseppe Cirino ,&nbsp;Fabio De Iaco ,&nbsp;Silvia De Rosa ,&nbsp;Francesco Dentali ,&nbsp;Paola Facchin ,&nbsp;Ennio Giulio Favalli ,&nbsp;Francesco Fiorin ,&nbsp;Antonino Giarratano ,&nbsp;Claudia Laterza ,&nbsp;Francesco Macrì ,&nbsp;Annamaria De Luca","doi":"10.1016/j.phrs.2025.107714","DOIUrl":"10.1016/j.phrs.2025.107714","url":null,"abstract":"<div><div>Atypical Hemolytic Uremic Syndrome (aHUS) is a severe, systemic, rare disease (RD) that can occur in people of all ages, and is associated with high rates of morbidity and mortality. Because the management of patients with aHUS can be difficult, more effective strategies should be implemented. Faculty members from several Italian Scientific Societies, Patient Associations and Regional Institutional Experts on RDs met to discuss aHUS management within a multidisciplinary team (MDT), using a Delphi process to develop consensus recommendations. Consensus (≥70 % agreement by faculty members) was reached on 51 statements with the aim of improving patient management and outcomes. These statements provide a unified framework for the differential diagnosis of aHUS, prompt recognition of the pathology, referral to RD reference centers, selecting between treatment relapse prevention measures options, patient management by a MDT and improving the overall awareness of aHUS. Despite the broad scope of the consensus statements, several unmet needs in the management of patients with aHUS were identified, including diagnostic suspicion, rapid genetic investigations, regular review of the centers of expertise (considering the number of treated patients), permanent clinical referral in treatment centers and widespread expertise among adult and pediatric specialists. We hope that this standardized framework will form the basis of the “digital ecosystem” concept and development of possible information technology solutions to assist the MDT involved in the management of patients with aHUS.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"216 ","pages":"Article 107714"},"PeriodicalIF":9.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}