Pharmacology & Therapeutics最新文献_第10页

Unfolded protein responses: Dynamic machinery in wound healing 未折叠蛋白反应：伤口愈合的动态机制。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-01-17 DOI: 10.1016/j.pharmthera.2025.108798

Morgan Minjares , Pattaraporn Thepsuwan , Kezhong Zhang , Jie-Mei Wang

{"title":"Unfolded protein responses: Dynamic machinery in wound healing","authors":"Morgan Minjares , Pattaraporn Thepsuwan , Kezhong Zhang , Jie-Mei Wang","doi":"10.1016/j.pharmthera.2025.108798","DOIUrl":"10.1016/j.pharmthera.2025.108798","url":null,"abstract":"<div><div>Skin wound healing is a dynamic process consisting of multiple cellular and molecular events that must be tightly coordinated to repair the injured tissue efficiently. The healing pace is decided by the type of injuries, the depth and size of the wounds, and whether wound infections occur. However, aging, comorbidities, genetic factors, hormones, and nutrition also impact healing outcomes. During wound healing, cells undergo robust processes of synthesizing new proteins and degrading multifunctional proteins. This imposes an increasing burden on the endoplasmic reticulum (ER), causing ER stress. Unfolded protein response (UPR) represents a collection of highly conserved stress signaling pathways originated from the ER to maintain protein homeostasis and modulate cell physiology. UPR is known to be beneficial for tissue healing. However, when excessive ER stress exceeds ER's folding potential, UPR pathways trigger cell apoptosis, interrupting tissue regeneration. Understanding how UPR pathways modulate the skin's response to injuries is critical for new interventions toward the control of acute and chronic wounds. Herein, in this review, we focus on the participation of the canonical and noncanonical UPR pathways during different stages of wound healing, summarize the available evidence demonstrating UPR's unique position in balancing homeostasis and pathophysiology of healing tissues, and highlight the understudied areas where therapeutic opportunities may arise.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"267 ","pages":"Article 108798"},"PeriodicalIF":12.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

G protein-coupled purinergic P2Y receptors in infectious diseases G蛋白偶联嘌呤能P2Y受体在传染病中的作用。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-01-13 DOI: 10.1016/j.pharmthera.2025.108796

Letícia de Almeida Carvalho , Vinícius Santos Alves , Robson Coutinho-Silva , Luiz Eduardo Baggio Savio

{"title":"G protein-coupled purinergic P2Y receptors in infectious diseases","authors":"Letícia de Almeida Carvalho , Vinícius Santos Alves , Robson Coutinho-Silva , Luiz Eduardo Baggio Savio","doi":"10.1016/j.pharmthera.2025.108796","DOIUrl":"10.1016/j.pharmthera.2025.108796","url":null,"abstract":"<div><div>The purinergic P2Y receptors comprise eight G-coupled receptor (GPCR) subtypes already identified (P2Y<sub>1</sub>, P2Y<sub>2</sub>, P2Y<sub>4</sub>, P2Y<sub>6</sub>, P2Y<sub>11</sub>, P2Y<sub>12</sub><sub>–</sub><sub>14</sub>). P2Y receptor physiological agonists are extracellular purine and pyrimidine nucleotides such as ATP (Adenosine triphosphate), ADP (Adenosine diphosphate), UTP (Uridine triphosphate), UDP (Uridine diphosphate), and UDP-glucose. These receptors are expressed in almost all cells. P2Y receptors are found in immune cells, such as macrophages, neutrophils, mast cells, dendritic cells, and lymphocytes. P2Y receptors play essential roles in inflammation and are involved in several cell processes, including efferocytosis, phagocytosis, chemotaxis, degranulation, killing pathogens, cytokine production, and platelet aggregation. These processes underpin immune responses against pathogens. Therefore, here we discuss P2Y receptor pharmacology and mechanisms triggered by the activation of these receptors in virus, bacteria, and parasite infections. In addition, we highlight the therapeutical potential of P2Y receptors for developing new pharmacological strategies to modulate inflammation and disease outcomes in pathogen infections.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"267 ","pages":"Article 108796"},"PeriodicalIF":12.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Healing action of Interleukin-4 (IL-4) in acute and chronic inflammatory conditions: Mechanisms and therapeutic strategies 白介素-4 （IL-4）在急慢性炎症中的愈合作用：机制和治疗策略。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-01-01 DOI: 10.1016/j.pharmthera.2024.108760

Kai Pan , Qiong Li , Zhikun Guo , Zongjin Li

{"title":"Healing action of Interleukin-4 (IL-4) in acute and chronic inflammatory conditions: Mechanisms and therapeutic strategies","authors":"Kai Pan , Qiong Li , Zhikun Guo , Zongjin Li","doi":"10.1016/j.pharmthera.2024.108760","DOIUrl":"10.1016/j.pharmthera.2024.108760","url":null,"abstract":"<div><div>Interleukin-4 (IL-4), which is traditionally associated with inflammation, has emerged as a key player in tissue regeneration. Produced primarily by T-helper 2 (Th2) and other immune cells, IL-4 activates endogenous lymphocytes and promotes M2 macrophage polarization, both of which are crucial for tissue repair. Moreover, IL-4 stimulates the proliferation and differentiation of various cell types, contributing to efficient tissue regeneration, and shows promise for promoting tissue regeneration after injury. This review explores the multifaceted roles of IL-4 in tissue repair, summarizing its mechanisms and potential for clinical application. This review delves into the multifaceted functions of IL-4, including its immunomodulatory effects, its involvement in tissue regeneration, and its potential therapeutic applications. We discuss the mechanisms underlying IL-4-induced M2 macrophage polarization, a crucial process for tissue repair. Additionally, we explore innovative strategies for delivering IL-4, including gene therapy, protein-based therapies, and cell-based therapies. By leveraging the regenerative properties of IL-4, we can potentially develop novel therapies for various diseases, including chronic inflammatory disorders, autoimmune diseases, and organ injuries. While early research has shown promise for the application of IL-4 in regenerative medicine, further studies are needed to fully elucidate its therapeutic potential and optimize its use.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108760"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The intricate interactions between inflammasomes and bacterial pathogens: Roles, mechanisms, and therapeutic potentials 炎性体与细菌病原体之间错综复杂的相互作用：作用、机制和治疗潜力。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2025-01-01 DOI: 10.1016/j.pharmthera.2024.108756

Jin Kyung Kim , Asmita Sapkota , Taylor Roh , Eun-Kyeong Jo

{"title":"The intricate interactions between inflammasomes and bacterial pathogens: Roles, mechanisms, and therapeutic potentials","authors":"Jin Kyung Kim , Asmita Sapkota , Taylor Roh , Eun-Kyeong Jo","doi":"10.1016/j.pharmthera.2024.108756","DOIUrl":"10.1016/j.pharmthera.2024.108756","url":null,"abstract":"<div><div>Inflammasomes are intracellular multiprotein complexes that consist of a sensor, an adaptor, and a caspase enzyme to cleave interleukin (IL)-1β and IL-18 into their mature forms. In addition, caspase-1 and -11 activation results in the cleavage of gasdermin D to form pores, thereby inducing pyroptosis. Activation of the inflammasome and pyroptosis promotes host defense against pathogens, whereas dysregulation of the inflammasome can result in various pathologies. Inflammasomes exhibit versatile microbial signal detection, directly or indirectly, through cellular processes, such as ion fluctuations, reactive oxygen species generation, and the disruption of intracellular organelle function; however, bacteria have adaptive strategies to manipulate the inflammasome by altering microbe-associated molecular patterns, intercepting innate pathways with secreted effectors, and attenuating inflammatory and cell death responses. In this review, we summarize recent advances in the diverse roles of the inflammasome during bacterial infections and discuss how bacteria exploit inflammasome pathways to establish infections or persistence. In addition, we highlight the therapeutic potential of harnessing bacterial immune subversion strategies against acute and chronic bacterial infections. A more comprehensive understanding of the significance of inflammasomes in immunity and their intricate roles in the battle between bacterial pathogens and hosts will lead to the development of innovative strategies to address emerging threats posed by the expansion of drug-resistant bacterial infections.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108756"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimizing drug therapies in cardiac amyloidosis 优化心脏淀粉样变性的药物疗法。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108758

Mohamed Younis, Ikechukwu Ogbu, Dinesh K. Kalra

{"title":"Optimizing drug therapies in cardiac amyloidosis","authors":"Mohamed Younis, Ikechukwu Ogbu, Dinesh K. Kalra","doi":"10.1016/j.pharmthera.2024.108758","DOIUrl":"10.1016/j.pharmthera.2024.108758","url":null,"abstract":"<div><div>Cardiac amyloidosis (CA) is a form of infiltrative, restrictive cardiomyopathy that presents a diagnostic and therapeutic challenge in clinical practice. Historically, it has led to poor prognosis due to limited treatment options. However, advancements in disease awareness, diagnostic tools, and management approaches have led to the beginning of an era characterized by earlier diagnosis and a broader range of treatments. This article examines the advances in treating the two primary forms of cardiac amyloidosis: transthyretin cardiac amyloidosis (ATTR-CA) and light chain mediated cardiac amyloidosis (AL-CA). It highlights therapies for ATTR-CA that focus on interrupting the process of amyloid fibril formation. These therapies include transthyretin stabilizers, gene silencers, and monoclonal antibodies, which have shown the potential to improve patient outcomes and survival rates significantly. As of this writing, tafamidis is the sole Food and Drug Administration (FDA)--approved drug for ATTR-CA; however, experts anticipate several other drugs will gain approval within 1–2 years. Treatment strategies for AL-CA typically involve chemotherapy to inhibit the clonal cell type responsible for excessive AL amyloid fibril production. The prognosis for both types of amyloidosis primarily depends on how much the heart is affected, with most deaths occurring due to progressive heart failure. Effective care for CA patients requires collaboration among specialists from multiple disciplines, such as heart failure cardiology, electrophysiology, hematology/oncology, nephrology, neurology, pharmacology, and palliative care.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108758"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pathology of idiopathic pulmonary fibrosis with particular focus on vascular endothelium and epithelial injury and their therapeutic potential 特发性肺纤维化的病理学，特别关注血管内皮和上皮损伤及其治疗潜力。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108757

Wenying Lu , Alan Teoh , Maddison Waters , Greg Haug , Ilma Shakeel , Imtaiyaz Hassan , Affan Mahmood Shahzad , Anna-Karin Larsson Callerfelt , Lucilla Piccari , Sukhwinder Singh Sohal

{"title":"Pathology of idiopathic pulmonary fibrosis with particular focus on vascular endothelium and epithelial injury and their therapeutic potential","authors":"Wenying Lu , Alan Teoh , Maddison Waters , Greg Haug , Ilma Shakeel , Imtaiyaz Hassan , Affan Mahmood Shahzad , Anna-Karin Larsson Callerfelt , Lucilla Piccari , Sukhwinder Singh Sohal","doi":"10.1016/j.pharmthera.2024.108757","DOIUrl":"10.1016/j.pharmthera.2024.108757","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) remains a challenging disease with no drugs available to change the trajectory. It is a condition associated with excessive and highly progressive scarring of the lungs with remodelling and extracellular matrix deposition. It is a highly “destructive” disease of the lungs. The diagnosis of IPF is challenging due to continuous evolution of the disease, which also makes early interventions very difficult. The role of vascular endothelial cells has not been explored in IPF in great detail. We do not know much about their contribution to arterial or vascular remodelling, extracellular matrix changes and contribution to pulmonary hypertension and lung fibrosis in general. Endothelial to mesenchymal transition appears to be central to such changes in IPF. Similarly, for epithelial changes, the process of epithelial to mesenchymal transition seem to be the key both for airway epithelial cells and type-2 pneumocytes. We focus here on endothelial and epithelial cell changes and its contributions to IPF. In this review we revisit the pathology of IPF, mechanistic signalling pathways, clinical definition, update on diagnosis and new advances made in treatment of this disease. We discuss ongoing clinical trials with mode of action. A multidisciplinary collaborative approach is needed to understand this treacherous disease for new therapeutic targets.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108757"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Collateral lethality: A unique type of synthetic lethality in cancers 附带致死率：癌症中一种独特的合成致死率。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-23 DOI: 10.1016/j.pharmthera.2024.108755

Zichen Zhao , Lingling Zhu , Yu Luo , Heng Xu , Yan Zhang

{"title":"Collateral lethality: A unique type of synthetic lethality in cancers","authors":"Zichen Zhao , Lingling Zhu , Yu Luo , Heng Xu , Yan Zhang","doi":"10.1016/j.pharmthera.2024.108755","DOIUrl":"10.1016/j.pharmthera.2024.108755","url":null,"abstract":"<div><div>Genetic interactions play crucial roles in cell-essential functions. Intrinsic genetic defects in tumors typically involve gain-of- and loss-of-function mutations in tumor suppressor genes (TSGs) and oncogenes, respectively, providing potential antitumor vulnerabilities. Moreover, tumor cells with TSG deficiencies exhibit heightened sensitivity to the inhibition of compensatory pathways. Synthetic and collateral lethality are two strategies used for exploiting novel drug targets in multiple types of cancer. Collateral lethality is a unique type of synthetic lethality that occurs when passenger genes are co-deleted in neighboring TSGs. Although synthetic lethality has already been successfully demonstrated in clinical practice, antitumor therapeutics based on collateral lethality are predominantly still in the preclinical phase. Therefore, screening for potential genetic interactions within the cancer genome has emerged as a promising approach for drug development. Here, the two conceptual therapeutic strategies that involve the deletion or inactivation of cancer-specific TSGs are discussed. Moreover, existing approaches for screening and identifying potential gene partners are also discussed. Particularly, this review highlights the current advances of “collateral lethality” in the preclinical phase and addresses the challenges involved in translating them into therapeutic applications. This review provides insights into these strategies as new opportunities for the development of personalized antitumor therapies.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108755"},"PeriodicalIF":12.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation 有利于消除炎症的脂质介质和创新疗法。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-18 DOI: 10.1016/j.pharmthera.2024.108753

Hong Yong Peh , Jianmin Chen

{"title":"Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation","authors":"Hong Yong Peh , Jianmin Chen","doi":"10.1016/j.pharmthera.2024.108753","DOIUrl":"10.1016/j.pharmthera.2024.108753","url":null,"abstract":"<div><div>This review summarizes findings presented at the 19th World Congress of Basic & Clinical Pharmacology 2023 (Glasgow, Scotland, July 3rd to 7th, 2023) from 8 speakers in the field of resolution of inflammation, resolution pharmacology and resolution biology. It is now accepted that the acute inflammatory response is protective to defend the host against infection or tissue injury. Acute inflammation is self-limited and programmed to be limited in space and time: this is achieved through endogenous resolution processes that ensure return to homeostasis. Resolution is brought about by agonist mediators that include specialized pro-resolving lipid mediators (SPMs) and pro-resolving proteins and peptides such as annexin A1 and angiotensin-(1–7), all acting to initiate anti-inflammatory and pro-resolving processes. If the inflammatory reaction remains unchecked through dysfunctional resolution mechanism, it can become chronic and contribute to a plethora of human diseases, including respiratory, cardiovascular, metabolic, allergic diseases, and arthritis. Herein, we discuss how non-resolving inflammation plays a role in the pathogenesis of these diseases. In addition to SPMs, we highlight the discovery, biosynthesis, biofunctions, and latest research updates on innovative therapeutics (including annexin-A1 peptide-mimetic RTP-026, small molecule FPR2 agonist BM-986235/LAR-1219, biased agonist for FPR1/FPR2 Cmpd17b, lipoxin mimetics AT-01-KG and AT-02-CT, melanocortin receptor agonist AP1189, gold nanoparticles, angiotensin-(1–7), and CD300a) that can promote resolution of inflammation directly or through modulation of SPMs production. Drug development strategies based on the biology of the resolution of inflammation can offer novel therapeutic means and/or add-on therapies for the treatment of chronic diseases.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108753"},"PeriodicalIF":12.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges 天然产品纳米微粒的药效学和药理学机制：发展与挑战。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-18 DOI: 10.1016/j.pharmthera.2024.108754

Junzhe Zhang , Huanhuan Pang , Huan Tang , Qingchao Tu , Fei Xia , Hao Zhang , Yuqing Meng , Guang Han , Jigang Wang , Chong Qiu

{"title":"The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges","authors":"Junzhe Zhang , Huanhuan Pang , Huan Tang , Qingchao Tu , Fei Xia , Hao Zhang , Yuqing Meng , Guang Han , Jigang Wang , Chong Qiu","doi":"10.1016/j.pharmthera.2024.108754","DOIUrl":"10.1016/j.pharmthera.2024.108754","url":null,"abstract":"<div><div>Natural products such as Traditional Chinese Medicines (TCMs) show great advantages in the treatment and prevention of diseases, but the unclear effective ingredients and mechanisms are key obstacles to restrict their rapid development. Under the guidance of the theoretical guidance of reductionism and the theoretical of allopathic medicine, some researches have indeed achieved some breakthrough results. However, these incomplete methods mainly limited to direct actions or indirect actions (such as the intermediated substances mediated cross-organ or cross-system regulation) mechanism of single active ingredient derived from natural products, which are often inconsistent with Systemism and Harmonizing Medicine and make it difficult to reasonably explain the pharmacodynamics and pharmacological mechanism of most natural products. Actually, effective pharmaceutical ingredients often do not exist in the form of free monomers, but prefer to assembly nanovesicles (NVs) for a combinational pharmacological effect, mainly including self-assembled nanoparticles (SANs) and exosome-like nanoparticles (ELNs). These developments of NVs-based application are a good supplement to existing pharmacological mechanism research. Hence, this review focuses on the developments and strategies of the pharmacodynamics and pharmacological mechanism of NVs-based TCMs under the combining theory of traditional Chinese and western medicine. On this basis, a novel “multidimensional combination” research approach is proposed firstly, which will provide new strategies and directions for breaking through the bottleneck of pharmacological mechanism research, and promote the clinical application of innovative natural products including TCMs.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108754"},"PeriodicalIF":12.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Exploring the landscape of post-translational modification in drug discovery 探索药物发现中翻译后修饰的全貌。

IF 12 1区医学

Pharmacology & Therapeutics Pub Date : 2024-11-16 DOI: 10.1016/j.pharmthera.2024.108749

Yuhao Cao , Tianyi Yu , Ziang Zhu , Yuanjiao Zhang , Shanliang Sun , Nianguang Li , Chunyan Gu , Ye Yang

{"title":"Exploring the landscape of post-translational modification in drug discovery","authors":"Yuhao Cao , Tianyi Yu , Ziang Zhu , Yuanjiao Zhang , Shanliang Sun , Nianguang Li , Chunyan Gu , Ye Yang","doi":"10.1016/j.pharmthera.2024.108749","DOIUrl":"10.1016/j.pharmthera.2024.108749","url":null,"abstract":"<div><div>Post-translational modifications (PTMs) play a crucial role in regulating protein function, and their dysregulation is frequently associated with various diseases. The emergence of epigenetic drugs targeting factors such as histone deacetylases (HDACs) and histone methyltransferase enhancers of zeste homolog 2 (EZH2) has led to a significant shift towards precision medicine, offering new possibilities to overcome the limitations of traditional therapeutics. In this review, we aim to systematically explore how small molecules modulate PTMs. We discuss the direct targeting of enzymes involved in PTM pathways, the modulation of substrate proteins, and the disruption of protein-enzyme interactions that govern PTM processes. Additionally, we delve into the emerging strategy of employing multifunctional molecules to precisely regulate the modification levels of proteins of interest (POIs). Furthermore, we examine the specific characteristics of these molecules, evaluating their therapeutic benefits and potential drawbacks. The goal of this review is to provide a comprehensive understanding of PTM-targeting strategies and their potential for personalized medicine, offering a forward-looking perspective on the evolution of precision therapeutics.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"265 ","pages":"Article 108749"},"PeriodicalIF":12.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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