International journal of drug discovery and pharmacology最新文献

{"title":"Mechanism of Action and Target Detection of Danshen & Hawthorn in the Treatment of Non-Alcoholic Fatty Liver Disease Based on Network Pharmacology and Virtual Docking Simulation","authors":"Zirong Zhou, Wenxia Tang, Qinghao Jiao, Yaxing Li, Yi Yang, Hui Li, Jie Yu, Songsong Wang","doi":"10.53941/ijddp.2026.100008","DOIUrl":"https://doi.org/10.53941/ijddp.2026.100008","url":null,"abstract":"Using network pharmacology, we identified the active ingredients and potential targets of the “Danshen & Hawthorn” herb pair for treating NAFLD. Disease targets for NAFLD were retrieved from relevant databases, and a “herb-ingredient-target” network was constructed. KEGG pathway analysis revealed that the therapeutic mechanism was associated with the IL-17, TNF, and PPAR signaling pathways, among others. Experimental validation in both in vitro (cellular model of steatosis) and in vivo (zebrafish model of NAFLD) models demonstrated that the herbal extract alleviated high-fat-induced damage. Virtual molecular docking of the top-ranked compound-target pairs identified potential key binding residues: PHE 207, TYR 134, HIS 25, GLY 143, and SER 53 for Pparg-Quercetin; ILE 317, MET 355, and PHE 273 for Ppara-Eburicoic acid; and ILE 354, PHE 351, TYR 314, SER 280, and HIS 440 for Hmox1-Dehydroeburicoic acid. In conclusion, the “Danshen & Hawthorn” herb pair ameliorates NAFLD by modulating the expression of PPARα, TNF-α, and IL-17, thereby reducing inflammation and lipid accumulation. This study provides molecular-level insights by identifying critical amino acid residues for target engagement.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://media.sciltp.com/articles/2604003671/2604003671.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147879318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects and Mechanism of Guilu Bushen Pill in the Treatment of Osteoporosis Model in Ovariectomized Rats","authors":"Ximing Peng, Junjie Huang, Peifang Lai, Xiaorong Zhang, Mingdeng Guan, Xin Hu, Yichen Ma, Meiqi Ji, Haiyan Gong, Chunhong Li, Xiuping Chen, Huaqian Wang","doi":"10.53941/ijddp.2025.100016","DOIUrl":"https://doi.org/10.53941/ijddp.2025.100016","url":null,"abstract":"Guilu Bushen Pill (GLBSW) is a traditional Chinese medicine formulation recognized for its kidney-nourishing effects. According to traditional Chinese medicine theory, kidney health is closely linked to bone strength. This study aims to investigate the effects of GLBSW on osteoblast differentiation using SaoS-2 cells, as well as its therapeutic potential in an ovariectomy-induced osteoporosis (OVX) rat model. In vitro results indicate that GLBSW significantly promotes the differentiation of SaoS-2 cells, while in vivo experiments demonstrate its effectiveness in alleviating osteoporosis in OVX rats by enhancing bone mineral density (BMD), improving both the quantity and quality of bone trabeculae, and maintaining calcium and phosphorus levels in bone. Metabolomic analysis of serum metabolites suggests that the therapeutic effects of GLBSW may be associated with the modulation of pyruvate and arachidonic acid metabolism. In conclusion, these findings underscore the potential of GLBSW in the treatment of osteoporosis through the regulation of bone formation and energy metabolism.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147911873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Re Ameliorates Cardiac Hypertrophy by Regulating CaSR-Mediated Signaling Pathway","authors":"Panpan Chen, Mubo Liu, Hong Xiao, Ting Luo, Hong Ling, Xiaoyan Chen, Zongli Li, Shangfu Xu, Li Zheng, Jiang Deng","doi":"10.53941/ijddp.2025.100006","DOIUrl":"https://doi.org/10.53941/ijddp.2025.100006","url":null,"abstract":"Article Ginsenoside Re Ameliorates Cardiac Hypertrophy by Regulating CaSR-Mediated Signaling Pathway Panpan Chen 1,2,3, Mubo Liu 1,2,3,4, Hong Xiao 1,2,4, Ting Luo 1,2,4, Hong Ling 1,2,4, Xiaoyan Chen 5, Zongli Li 4, Shangfu Xu 1,2, Zheng Li 1,2,4 and Jiang Deng 1,2,4,* 1 Key Laboratory of Basic Pharmacology of Ministry of Education, Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China 2 Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi 563000, China. 3 The Affiliated Aerospace Hospital of Zunyi Medical University, Guizhou Aerospace Hospital, Zunyi 563000, China 4 Department of Pharmacology, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China 5 Department of Pathophysiology, Zunyi Medical University, Zunyi 563000, China * Correspondence: dengjiang1225@sina.com; Tel.: +86-851-2864-3411; Fax: +86-851-2864-2406 Received: 31 August 2024; Revised: 17 September 2024; Accepted: 19 September 2024; Published: 5 March 2025 Abstract: Cardiac hypertrophy is a compensatory response to pathological stimuli. Recent studies have suggested that calcium-sensing receptor (CaSR) plays an important role in the development of cardiac hypertrophy. Ginsenoside Re (Re) is a monoconstituent of the ginseng plant. Many studies have shown that Re has various beneficial pharmacological effects on the cardiovascular system. It remains uncertain if Re have an anti-cardiac hypertrophic effect through the modulation of the CaSR-mediated signaling pathway. In this research, we employed a rat model of cardiac hypertrophy to investigate the relationship between Re and CaSR. Significant reductions in blood pressure, left ventricle hypertrophic indexes, cross-sectional area of cardiomyocytes, and levels of the β-myosin heavy chain and atrial natriuretic peptide were observed in spontaneously hypertensive rats (SHR) after Re administration. In addition, Re improved cardiac structure and function in SHR. Furthermore, Re inhibited CaSR, calcineurin (CaN), nuclear factor of activated T cells 3 (NFAT3), phosphorylated zinc finger transcription factor 4 (p-GATA4), protein kinase C-β (PKC-β), rapidly accelerated fibrosarcoma-1 (Raf-1), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2). It also increased the expression of p-NFAT3 and mitogen-activated protein kinase phosphatase-1 (MKP-1). These findings suggest that Re has beneficial effects on cardiac hypertrophy in SHR. The mechanisms underlying these effects are the regulation of the PKC-MAPK axis and the CaSR-mediated signaling pathway.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"1 1","pages":"100006-100006"},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciltp.com/journals/ijddp/article/download/825/534","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147887399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rho/ROCK Pathway as a Therapeutic Target in Multiple Diseases.","authors":"Zixiu Cheng, Shannon Erhardt, Jun Wang","doi":"10.53941/ijddp.2025.100018","DOIUrl":"10.53941/ijddp.2025.100018","url":null,"abstract":"<p><p>The Rho/ROCK (Rho-associated coiled-coil-containing protein kinase) signaling pathway plays a pivotal role in regulating diverse cellular processes, including cytoskeletal organization, cell migration, proliferation, and apoptosis. Dysregulation of this pathway has been implicated in the pathogenesis of various diseases, such as cardiovascular disorders, cancer, neurological conditions, and fibrotic diseases. Accumulating evidence supports the therapeutic potential of targeting Rho/ROCK, with several inhibitors currently under investigation or in clinical use. This review summarizes the molecular mechanisms underlying Rho/ROCK signaling, explores its involvement in disease progression, and discusses recent advances in the development of and the clinical application of ROCK inhibitors as promising therapeutic agents.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12687578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145727927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Receptor-Targeted Therapy for Metabolic Dysfunction-Associated Steatotic Liver Disease.","authors":"Yachao Zhou, Zhaojian Liu, Donghai Cui, Xingyun Qi, Huiliang Zhang","doi":"10.53941/ijddp.2025.100024","DOIUrl":"10.53941/ijddp.2025.100024","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting over 25% of the global population. Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced stage of MASLD, characterized by hepatic steatosis accompanied by inflammation, hepatocellular injury, and fibrosis. Despite its high prevalence and clinical significance, effective treatments for MASLD and MASH remain limited, largely due to the complexity of the underlying pathophysiological mechanism, which remains not yet fully understood. Nuclear receptors (NRs) are a superfamily of transcription factors and play a key role in regulating lipid metabolism, glucose homeostasis, inflammation, and fibrosis, all of which are central to MASLD progression. Consequently, NRs have emerged as promising molecular targets for MASLD treatment, and a few new NR-targeted drugs were approved recently, including thyroid hormone receptor-β (THR-β) agonist resmetirom, the dual peroxisome proliferator-activated receptor (PPAR)-α/γ agonist saroglitazar. Moreover, several NR-targeted drugs are under clinical trials. In this mini-review, we summarize the recent progress of the mechanisms of key NRs in the pathogenesis of MASLD, and discuss the advances in nuclear receptor-targeted therapy, with emphasis on THR-β, PPARs, and the non-bile acid farnesoid X receptor (FXR).</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"4 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13048784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147625225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoints Are New Therapeutic Targets in Regulating Cardio-, and Cerebro-Vascular Diseases and CD4⁺Foxp3⁺ Regulatory T Cell Immunosuppression.","authors":"Ying Shao, William Y Yang, Gayani Nanayakkara, Fatma Saaoud, Mohammed Ben Issa, Keman Xu, Yifan Lu, Xiaohua Jiang, Sadia Mohsin, Hong Wang, Xiaofeng Yang","doi":"10.53941/ijddp.2024.100022","DOIUrl":"10.53941/ijddp.2024.100022","url":null,"abstract":"<p><p>Although previous reviews explored the roles of selected immune checkpoints (ICPs) in cardiovascular diseases (CVD) and cerebrovascular diseases from various perspectives, many related aspects have yet to be thoroughly reviewed and analyzed. Our comprehensive review addresses this gap by discussing the cellular functions of ICPs, focusing on the tissue-specific and microenvironment-localized transcriptomic and posttranslational regulation of ICP expressions, as well as their functional interactions with metabolic reprogramming. We also analyze how 14 pairs of ICPs, including CTLA-4/CD86-CD80, PD1-PDL-1, and TIGIT-CD155, regulate CVD pathogenesis. Additionally, the review covers the roles of ICPs in modulating CD4⁺Foxp3⁺ regulatory T cells (Tregs), T cells, and innate immune cells in various CVDs and cerebrovascular diseases. Furthermore, we outline seven immunological principles to guide the development of new ICP-based therapies for CVDs. This timely and thorough analysis of recent advancements and challenges provide new insights into the role of ICPs in CVDs, cerebrovascular diseases and Tregs, and will support the development of novel therapeutics strategies for these diseases.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Roles of HIF-1, HO-1, GLUT-1 and GLUT-4 in Myocardial Protection.","authors":"Lionel Chong, Nicholas Dushaj, Ani Rakoubian, Johnathan Yarbro, Satoru Kobayashi, Qiangrong Liang","doi":"10.53941/ijddp.2024.100016","DOIUrl":"10.53941/ijddp.2024.100016","url":null,"abstract":"<p><p>Cardiomyocytes are highly dependent on oxygen for optimal function. Disruption of oxygen availability, as in the case of ischemic heart disease, can significantly impair heart function. Moreover, comorbidities like diabetes, hyperlipidemia, and hypertension can exacerbate ischemic cardiac injury. However, cardiomyocytes possess inherent protective mechanisms that can be activated to enhance myocardial survival under such conditions. Understanding the functions and regulatory mechanisms of these cardioprotective genes is crucial for advancing our knowledge of cardiovascular health and for developing therapeutic strategies. This review examines the intricate mechanisms of cardioprotection, with a focus on key genes and proteins, including hypoxia-inducible factor-1 (HIF-1), heme oxygenase-1 (HO-1), glucose transporter 1 (GLUT-1), and GLUT-4. In addition, the review explores the roles and regulation of these factors in the heart under ischemic stress, shedding light on their relevance in conditions like diabetes, hypertension, and hyperlipidemia/atherosclerosis. Moreover, it highlights the complex interplay among their mechanisms and suggests opportunities for developing targeted therapiesfor the treatment of ischemic heart disease, hypertension, and hyperlipidemia.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eupatorium Lindleyanum DC. Extract Protects against MPTP-induced Mouse of Parkinson’s Disease by Targeting Neuroinflammation","authors":"Yichi Zhang, Lu Yao, Xiaowen Zhang, Zhuo Yang, Yang Chen, Lingli Zheng, Yongzhe Zheng, Wei Yu, Nilufar Z. Mamadalieva, Bo Han, Pengfei Tu, R. F. Mukhamatkhanova, Ke‐Wu Zeng","doi":"10.53941/ijddp.2024.100009","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100009","url":null,"abstract":"Article Eupatorium Lindleyanum DC. Extract Protects against MPTP-induced Mouse of Parkinson’s Disease by Targeting Neuroinflammation Yichi Zhang 1, Lu Yao 1, Xiaowen Zhang 1, Zhuo Yang 1, Yang Chen 2, Lingli Zheng 1, Yongzhe Zheng 1, Wei Yu 2, Nilufar Z. Mamadalieva 3, Bo Han 2, Pengfei Tu 1, Rimma F. Mukhamatkhanova 3, and Kewu Zeng 1, * 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 2 School of Pharmacy/Key Laboratory of Xinjiang Phytomedicine Resource and Utilization, Shihezi University, Shihezi 832003, China 3 Institute of the Chemistry of Plant Substances AS RUz, Mirzo Ulugbek Str 77, Tashkent 100170, Uzbekistan * Correspondence: ZKW@bjmu.edu.cn Received: 10 May 2024; Revised: 14 May 2024; Accepted: 24 May 2024; Published: 6 June 2024 Abstract: Background: Neuroinflammation plays a vital role in the pathology of Parkinson’s disease (PD). Eupatorium lindleyanum DC. (EL) has previously reported to exert anti-inflammation activity. Methods: In the present study, we examined the effects of the EL extract (ELE) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and potential molecular mechanisms. The anti-neuroinflammation effect of ELE was also determined in lipopolysaccharide (LPS)-induced BV-2 cells in vitro. Moreover, the ELE-interacting target proteins were identified. And the bioinformatics analysis was performed based on the identified targets. Results: Our results showed that ELE significantly alleviated motor performance impairment and neuronal damage in MPTP-induced PD mice. In particular, ELE reversed MPTP-induced neuroinflammation via inhibiting microglial activation that was associated with progressive PD. Moreover, the anti-neuroinflammation effect of ELE was confirmed in LPS-induced BV-2 cells by detecting the release of pro-inflammatory factors such as nitric oxide (NO), interleukin-6 (Il-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Furthermore, the ELE- interacting target proteins were identified by affinity purification-mass spectrometry-based proteomics strategy. Then, AMP-activated protein kinase (AMPK) signaling pathway was enriched by kyoto encyclopedia of genes and genomes (KEGG) analysis. We found that ELE markedly increased AMPK phosphorylation and inhibited nuclear factor-κB (NF-κB) signal in BV-2 cells. Conclusion: Collectively, these results indicate that ELE may exert significant neuroprotective effects against PD via targeting neuroinflammation.","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"1 1","pages":"100009-100009"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://media.sciltp.com/articles/sciltp/392/pdf/6678dbed8ab0f.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147883655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrins as Drug Targets in Vascular and Related Diseases.","authors":"Emily Meredith, Martin A Schwartz","doi":"10.53941/ijddp.2024.100010","DOIUrl":"10.53941/ijddp.2024.100010","url":null,"abstract":"<p><p>Integrins are transmembrane receptors that, as critical participants in a vast range of pathological processes, are potential therapeutic targets. However, in only a few cases has the promise been realized by drug approval. In this review, we briefly review basic integrin biology and participation in disease, challenges in the development of safe, effective integrin-targeted therapies, and recent advances that may lead to progress.</p>","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"3 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibiting the Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Cascade in Cancer and the Heart: for Better or Worse, in Sickness and Health?","authors":"Angela Clerk","doi":"10.53941/ijddp.2024.100006","DOIUrl":"https://doi.org/10.53941/ijddp.2024.100006","url":null,"abstract":"Review\u0000Inhibiting the Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Cascade in Cancer and the Heart: for Better or Worse, in Sickness and Health?\u0000\u0000Angela Clerk *, Shona U Amadi, Samuel J Smith, and Peter H Sugden\u0000\u0000\u0000School of Biological Sciences, University of Reading, Reading RG6 6AS, UK\u0000* Correspondence: a.clerk@reading.ac.uk\u0000 \u0000Received: 3 April 2024; Revised: 27 April 2024; Accepted: 29 April 2024; Published: 23 May 2024\u0000 \u0000Abstract: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are the prototypic mitogen-activated protein kinases, first discovered and investigated in the context of cell division and their role in cancer. ERK1/2 are phosphorylated and activated by upstream kinases, MEK1/2 (also known as MKK1/2) that are in turn phosphorylated and activated by RAF kinases (RAF1, BRAF, ARAF), these being activated by small G proteins of the RAS family (HRAS, KRAS, NRAS). The oncogenic nature of the pathway has resulted in the generation of highly specific inhibitors that are successfully used to treat cancer, particularly melanoma. Those in clinical use currently inhibit some isoforms of RAS, RAF kinases and MEK1/2, with additional inhibitors of these kinases in clinical trials. New drugs are now entering the clinic to inhibit ERK1/2 themselves. The ERK1/2 cascade is also important in the heart. It promotes cardiomyocyte hypertrophy and cardioprotection to counter pathophysiological stresses, and plays a significant role in enhancing cardiac fibrosis with detrimental consequences for cardiac function. Here, we summarise the role of ERK1/2 signalling in cancer and the heart, we outline the development of ERK1/2 cascade inhibitors for cancer providing information on those that are approved as cancer treatments and those which are in clinical trials, and we discuss the known and predicted consequences of these ERK1/2 cascade inhibitors for the heart. Integral with this, we consider whether these drugs are necessarily detrimental to the heart or if/when they may be repurposed to prevent or treat heart failure.\u0000","PeriodicalId":94047,"journal":{"name":"International journal of drug discovery and pharmacology","volume":"46 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141103480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}