Acta Pharmaceutica Sinica. B最新文献

{"title":"Bacterial extracellular vesicles for gut microbiome–host communication and drug development","authors":"Dingfei Qian ,&nbsp;Peijun Xu ,&nbsp;Xinwei Wang ,&nbsp;Chong Du ,&nbsp;Xiao Zhao ,&nbsp;Jiaqi Xu","doi":"10.1016/j.apsb.2025.03.008","DOIUrl":"10.1016/j.apsb.2025.03.008","url":null,"abstract":"<div><div>As the intricate interplay between microbiota and the host garners increasing research attention, a significant parallel surge has emerged in the investigation of intestinal bacterial extracellular vesicles (BEVs). Most intestinal bacteria secrete BEVs, which harbor specific cargo molecules and exhibit diverse functions, encompassing interactions among bacteria themselves and between bacteria and the host. These interactions can either bolster host health or contribute to various pathologies. By integrating the characteristics of BEVs, we summarized the current research landscape, delving into the intricate interplay between BEVs and different diseases. Furthermore, we offer a succinct overview of the challenges faced in BEVs-based research, encompassing separation, detection, engineering for drug purposes, clinical diagnostics, safety, and future study. In essence, these summaries may serve as invaluable guides for BEVs as communication tools between the gut microbiome and host, ultimately propelling the discovery of novel studies and drug discovery.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1816-1840"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923351","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}

{"title":"Identification of a JAK–STAT–miR155HG positive feedback loop in regulating natural killer (NK) cells proliferation and effector functions","authors":"Songyang Li ,&nbsp;Yongjie Liu ,&nbsp;Xiaofeng Yin ,&nbsp;Yao Yang ,&nbsp;Xinjia Liu ,&nbsp;Jiaxing Qiu ,&nbsp;Qinglan Yang ,&nbsp;Yana Li ,&nbsp;Zhiguo Tan ,&nbsp;Hongyan Peng ,&nbsp;Peiwen Xiong ,&nbsp;Shuting Wu ,&nbsp;Lanlan Huang ,&nbsp;Xiangyu Wang ,&nbsp;Sulai Liu ,&nbsp;Yuxing Gong ,&nbsp;Yuan Gao ,&nbsp;Lingling Zhang ,&nbsp;Junping Wang ,&nbsp;Yafei Deng ,&nbsp;Youcai Deng","doi":"10.1016/j.apsb.2025.02.034","DOIUrl":"10.1016/j.apsb.2025.02.034","url":null,"abstract":"<div><div>The Janus kinase/signal transducers and activators of transcription (JAK–STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK–STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK–STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1922-1937"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923355","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}

{"title":"GRK2 activates TRAF2–NF-κB signalling to promote hyperproliferation of fibroblast-like synoviocytes in rheumatoid arthritis","authors":"Chenchen Han ,&nbsp;Liping Jiang ,&nbsp;Weikang Wang ,&nbsp;Shujun Zuo ,&nbsp;Jintao Gu ,&nbsp;Luying Chen ,&nbsp;Zhuo Chen ,&nbsp;Jiajie Kuai ,&nbsp;Xuezhi Yang ,&nbsp;Liang Xu ,&nbsp;Yang Ma ,&nbsp;Wei Wei","doi":"10.1016/j.apsb.2025.02.031","DOIUrl":"10.1016/j.apsb.2025.02.031","url":null,"abstract":"<div><div>G protein-coupled receptor kinase 2 (GRK2) participates in the phosphorylation and desensitization of G protein-coupled receptor (GPCR), impacting various biological processes such as inflammation and cell proliferation. Dysregulated expression and activity of GRK2 have been reported in multiple cells in rheumatoid arthritis (RA). However, whether and how GRK2 regulates synovial hyperplasia and fibroblast-like synoviocytes (FLSs) proliferation is poorly understood. In this study, we investigated the regulation of GRK2 and its biological function in RA. We found that GRK2 transmembrane activity was increased in FLSs of RA patients and collagen-induced arthritis (CIA) rats. Additionally, we noted a positive correlation between high GRK2 expression on the cell membrane and serological markers associated with RA and CIA. Immunoprecipitation–mass spectrometry and pull-down analyses revealed tumor necrosis factor receptor-associated factor 2 (TRAF2) as a novel substrate of GRK2. Furthermore, surface plasmon resonance (SPR) and molecular docking assays determined that the C-terminus of GRK2 binds to the C-terminus of TRAF2 at the Gln340 residue. GRK2 knockdown and the GRK2 inhibitor CP-25 attenuated synovial hyperplasia and FLS proliferation in CIA both <em>in vitro</em> and <em>in vivo</em> by decreasing GRK2 membrane expression and activity. Mechanistically, increased GRK2 transmembrane activity contributed to the recruitment of TRAF2 on the cell membrane, promoting GRK2–TRAF2 interactions that facilitate the recruitment of the E3 ubiquitin ligase TRIM47 to TRAF2. This enhanced TRAF2 Lys63 polyubiquitylation and induced nuclear factor (NF)-<em>κ</em>B activation, leading to synovial hyperplasia and abnormal proliferation of FLSs. Our study provides a mechanistic and preclinical rationale for further evaluation of GRK2 as a therapeutic target for RA.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 1956-1973"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923358","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}

{"title":"p52-ZER6/DAZAP1 axis promotes ferroptosis resistance and colorectal cancer progression via regulating SLC7A11 mRNA stabilization","authors":"Li Qiu ,&nbsp;Wenfang Li ,&nbsp;Lei Zhang ,&nbsp;Xia Zhang ,&nbsp;Hezhao Zhao ,&nbsp;Makoto Miyagishi ,&nbsp;Shourong Wu ,&nbsp;Vivi Kasim","doi":"10.1016/j.apsb.2025.02.013","DOIUrl":"10.1016/j.apsb.2025.02.013","url":null,"abstract":"<div><div>Resistance to ferroptosis, a form of regulated cell death caused by disruptions in iron ion and intracellular redox homeostasis, is closely related to tumorigenesis and tumor drug resistance; therefore, targeting ferroptosis-related pathways has garnered attention as a potential antitumor therapeutic strategy. However, the molecular mechanisms underlying ferroptosis resistance in tumor cells remain unknown. Zinc-finger estrogen receptor interaction clone 6 (ZER6) consists of two isoforms with distinct N-termini, p52-ZER6 and p71-ZER6. ZER6 is upregulated in tumors and promotes tumorigenic potential; however, whether ZER6 is involved in tumor cell ferroptosis resistance remains unknown. Herein, we identified p52-ZER6 as a novel regulator of tumor cell ferroptosis resistance. p52-ZER6 promotes the transcriptional activity of <em>DAZAP1</em>, an RNA-binding protein. DAZAP1, in turn, enhances the stability of <em>SLC7A11</em> mRNA by binding to its 3′-UTR region, thereby increasing SLC7A11 expression and cellular glutathione levels. This subsequently reduces lipid peroxide accumulation and enhances tumor cell ferroptosis resistance, eventually promoting tumorigenic potential. These findings reveal a new function of p52-ZER6 in regulating <em>SLC7A11</em> mRNA stability <em>via</em> DAZAP1, ultimately leading to ferroptosis resistance and tumorigenic potential. Additionally, we also suggest targeting p52-ZER6 as a potential strategy to promote the efficacy of ferroptosis-based antitumor therapies.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2039-2058"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923362","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}

{"title":"Design, molecular characterization and therapeutic investigation of a novel CCR8 peptide antagonist that attenuates acute liver injury by inhibiting infiltration and activation of macrophages","authors":"Eline Geervliet ,&nbsp;Sahil Arora ,&nbsp;Dagmara Donohue ,&nbsp;Carlos Antonio de Albuquerque Pinheiro ,&nbsp;Leon W.M.M. Terstappen ,&nbsp;Richard Schasfoort ,&nbsp;Julieta Paez ,&nbsp;Raj Kumar ,&nbsp;Ruchi Bansal","doi":"10.1016/j.apsb.2025.02.018","DOIUrl":"10.1016/j.apsb.2025.02.018","url":null,"abstract":"<div><div>During liver injury, intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C–C motif chemokine ligand/C–C motif chemokine receptor (CCL/CCR) axis including CCL1‒CCR8 axis, thereby contributing to liver inflammation. Numerous small molecular receptor antagonists, including R243, have been developed for targeting CCR8; however, these agents face challenges in clinical translation, potentially attributed to their poor pharmacokinetic profiles, lack of target specificity, and potential adverse effects. In this study, we designed four CCR8 antagonizing peptides (AP8i-AP8iv) and performed molecular characterization <em>in silico</em> and therapeutic investigation <em>in vitro</em> and <em>in vivo</em>. Based on <em>in silico</em> docking, molecular dynamic simulation using homology build model and <em>in-vitro</em> (competitive) binding studies, AP8ii (YEWRFYHG) evidenced highly favorable and selective interactions at the CCR8-active site. AP8ii inhibited CCL1-driven chemotaxis and LPS/IFN<em>γ</em>-induced pro-inflammatory activation of monocytes-macrophages <em>in vitro</em>. In a CCl₄-induced acute liver injury mouse model, AP8ii treatment decreased intrahepatic infiltration of circulating monocytes. Moreover, AP8ii reduced liver inflammation, as indicated by decreased F4/80, IL6 and iNOS expression, diminished ALT levels, and attenuated fibrosis, as indicated by reduced collagen-I expression. In conclusion, we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype, consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2114-2133"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923368","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}

{"title":"Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease","authors":"Zhipei Sang ,&nbsp;Shuheng Huang ,&nbsp;Wanying Tan ,&nbsp;Yujuan Ban ,&nbsp;Keren Wang ,&nbsp;Yufan Fan ,&nbsp;Hongsong Chen ,&nbsp;Qiyao Zhang ,&nbsp;Chanchan Liang ,&nbsp;Jing Mi ,&nbsp;Yunqi Gao ,&nbsp;Ya Zhang ,&nbsp;Wenmin Liu ,&nbsp;Jianta Wang ,&nbsp;Wu Dong ,&nbsp;Zhenghuai Tan ,&nbsp;Lei Tang ,&nbsp;Haibin Luo","doi":"10.1016/j.apsb.2025.02.030","DOIUrl":"10.1016/j.apsb.2025.02.030","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound <strong>8e</strong>, a selective reversible BuChE inhibitor (<em>eq</em>BuChE IC₅₀ = 0.049 μmol/L, <em>hu</em>BuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound <strong>8e</strong> demonstrated favorable blood–brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, <strong>8e</strong> exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, <strong>8e</strong> significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that <strong>8e</strong> markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound <strong>8e</strong> emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2134-2155"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923516","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}

{"title":"Synovial joints: The barometer of systemic inflammation","authors":"Jie Pan ,&nbsp;Qianqian Liu ,&nbsp;Yang Sun","doi":"10.1016/j.apsb.2024.12.025","DOIUrl":"10.1016/j.apsb.2024.12.025","url":null,"abstract":"","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 4","pages":"Pages 2287-2289"},"PeriodicalIF":14.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924443","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}

{"title":"Effective therapeutic targeting of tumor lineage plasticity in neuroendocrine prostate cancer by BRD4 inhibitors","authors":"Xiong Zhang ,&nbsp;Yatian Yang ,&nbsp;Hongye Zou ,&nbsp;Yang Yang ,&nbsp;Xingling Zheng ,&nbsp;Eva Corey ,&nbsp;Amina Zoubeidi ,&nbsp;Nicolas Mitsiades ,&nbsp;Ai-Ming Yu ,&nbsp;Yuanpei Li ,&nbsp;Hong-Wu Chen","doi":"10.1016/j.apsb.2025.01.007","DOIUrl":"10.1016/j.apsb.2025.01.007","url":null,"abstract":"<div><div>Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression. Through pharmacologically probing the function of epigenetic regulators in prostate cancer cells and organoids, we identified bromodomain protein BRD4 as a crucial player. Integrated ChIP-seq and RNA-seq analysis of tumors revealed, for the first time, that BRD4 directly activates hundreds of genes in the LP programs which include neurogenesis, axonogenesis, EMT and stem cells and key drivers such as <em>POU3F2</em> (BRN2), <em>ASCL1/2</em>, <em>NeuroD1</em>, <em>SOX2/9</em>, <em>RUNX1/2</em> and <em>DLL3</em>. Interestingly, BRD4 genome occupancy is reprogrammed by anti-AR drugs from facilitating AR function in CRPC cells to activating the LP programs and is facilitated by pioneer factor FOXA1. Significantly, we demonstrated that BRD4 inhibitor AZD5153, currently at clinical development, possesses potent activities in complete blockade of tumor growth of both <em>de novo</em> neuroendocrine prostate cancer (NEPC) and treatment-induced NEPC PDXs and that suppression of tumor expression of LP programs through reduction of local chromatin accessibility is the primary mechanism of action (MOA) by AZD5153. Together, our study revealed that BRD4 plays a fundamental role in direct activation of tumor LP programs and that its inhibitor AZD5153 is highly promising in effective treatment of the lethal forms of the diseases.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 3","pages":"Pages 1415-1429"},"PeriodicalIF":14.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776842","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}

{"title":"Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells","authors":"Weile Ye ,&nbsp;Pinglian Yang ,&nbsp;Mei Jin ,&nbsp;Jiami Zou ,&nbsp;Zhihua Zheng ,&nbsp;Yuanyuan Li ,&nbsp;Dongmei Zhang ,&nbsp;Wencai Ye ,&nbsp;Zunnan Huang ,&nbsp;Jiaojiao Wang ,&nbsp;Zhiping Liu","doi":"10.1016/j.apsb.2025.02.003","DOIUrl":"10.1016/j.apsb.2025.02.003","url":null,"abstract":"<div><div>Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in <em>Ampelopsis grossedentata</em> (<em>A. grossedentata</em>), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^−/−) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM’s anti-AAA action is linked to heme oxygenase (HO)-1 (<em>Hmox-1</em> for the rodent gene) and hypoxia-inducible factor (HIF)-1<em>α</em> in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific <em>Hmox1</em> knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of <em>Hmox-</em>1 by triggering the nuclear translocation and activation of HIF-1<em>α</em>, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 3","pages":"Pages 1514-1534"},"PeriodicalIF":14.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776319","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}

{"title":"Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon","authors":"Martin Kufa ,&nbsp;Vladimir Finger ,&nbsp;Ondrej Kovar ,&nbsp;Ondrej Soukup ,&nbsp;Carilyn Torruellas ,&nbsp;Jaroslav Roh ,&nbsp;Jan Korabecny","doi":"10.1016/j.apsb.2025.01.023","DOIUrl":"10.1016/j.apsb.2025.01.023","url":null,"abstract":"<div><div>Tuberculosis (TB), an infectious disease caused by the bacterium <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>), was responsible for the deaths of approximately 1.3 million people in 2022. In addition, 7.5 million new cases of TB have been reported. Present-day treatments require a daily dosing of a multiple-drug regimen for a minimum of six-month, but poor adherence and other factors often lead to treatment failure. Consequently, drug-resistant TB strains have become a growing concern, leading to more complex and expensive treatments. Promising drugs such as bedaquiline, delamanid, and pretomanid have been recently released, and 19 drug candidates are currently at different phases of clinical trials, addressing the problem of drug-resistant TB. Notwithstanding recent advances, the development of effective and safe drugs with novel mechanisms of action remains a challenge due to the unique nature of <em>Mtb</em>. Despite the persistent need for new treatments, TB research remains underfunded, highlighting the importance of collaborations between academia and the private sector in the advancement of anti-TB drug development. This review provides a perspective on the dynamic landscape of anti-TB drug discovery in recent years, offering hope for a more effective approach to combat this persistent global health threat.</div></div>","PeriodicalId":6906,"journal":{"name":"Acta Pharmaceutica Sinica. B","volume":"15 3","pages":"Pages 1311-1332"},"PeriodicalIF":14.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776902","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}