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Bioengineering of long-chain polyunsaturated fatty acids in oilseed crops Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-05-08 Zheng Yang, Yangyang Chen, Shijie Ma, Meng Zhang, Tong Tang, Chang Du
Long-chain polyunsaturated fatty acids (LC-PUFAs), especially very long-chain polyunsaturated fatty acids (VLC-PUFAs), are highly beneficial to human health including brain development, cardiovascular health and the immune system. Plant-derived edible oils serve as crucial dietary sources of PUFAs for humans. However, oilseed crops such as soybean, peanut, rapeseed, sesame and flax, generally contain
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EGFR controls transcriptional and metabolic rewiring in KRASG12D colorectal cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-05-06 Dana Krauß,Veronica Moreno-Viedma,Emi Adachi-Fernandez,Cristiano de Sá Fernandes,Jakob-Wendelin Genger,Ourania Fari,Bernadette Blauensteiner,Dominik Kirchhofer,Nikolina Bradaric,Valeriya Gushchina,Georgios Fotakis,Thomas Mohr,Ifat Abramovich,Inbal Mor,Martin Holcmann,Andreas Bergthaler,Arvand Haschemi,Zlatko Trajanoski,Juliane Winkler,Eyal Gottlieb,Maria Sibilia
Inhibition of the epidermal growth factor receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target to be co-inhibited with RAS inhibitors for effective treatment of KRAS mutant CRC. Here, we investigated the tumor cell-intrinsic contribution of EGFR in KRASG12D
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Corrigendum to “Opposite evolution of pathogenicity driven by in vivo wzc and wcaJ mutations in ST11-KL64 carbapenem-resistant Klebsiella pneumoniae” [Drug Resist. Updat. 66 (2023) 100891] Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-30 Jintao He, Qiucheng Shi, Zhifu Chen, Wang Zhang, Peng Lan, Qingye Xu, Huangdu Hu, Qiong Chen, Jianzhong Fan, Yan Jiang, Belinda Loh, Sebastian Leptihn, Quanming Zou, Jinyong Zhang, Yunsong Yu, Xiaoting Hua
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A novel model of glioblastoma recurrence to identify therapeutic vulnerabilities. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-28 Sara Lucchini,James G Nicholson,Xinyu Zhang,Jacob Househam,Yau Mun Lim,Maximilian Mossner,Thomas O Millner,Sebastian Brandner,Trevor Graham,Silvia Marino
Glioblastoma remains incurable and recurs in all patients. Here we design and characterize a novel induced-recurrence model in which mice xenografted with primary patient-derived glioma initiating/stem cells (GIC) are treated with a therapeutic regimen closely recapitulating patient standard of care, followed by monitoring until tumours recur (induced recurrence patient-derived xenografts, IR-PDX)
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Predictive modeling of glioblastoma recurrence for therapeutic target identification. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-28 Hrvoje Miletic,Thomas Daubon
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Spatial gene regulatory networks driving cell state transitions during human liver disease. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-25 Nigel L Hammond,Syed Murtuza Baker,Sokratia Georgaka,Ali Al-Anbaki,Elliot Jokl,Kara Simpson,Rosa Sanchez-Alvarez,Varinder S Athwal,Huw Purssell,Ajith K Siriwardena,Harry V M Spiers,Mike J Dixon,Leoma D Bere,Adam P Jones,Michael J Haley,Kevin N Couper,Nicoletta Bobola,Andrew D Sharrocks,Neil A Hanley,Magnus Rattray,Karen Piper Hanley
Liver fibrosis is a major cause of death worldwide. As a progressive step in chronic liver disease, fibrosis is almost always diagnosed too late with limited treatment options. Here, we uncover the spatial transcriptional landscape driving human liver fibrosis using single nuclei RNA and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to deconvolute multi-cell spatial transcriptomic profiling
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Long non-coding RNA LRTOR drives osimertinib resistance in non-small cell lung cancer by boosting YAP positive feedback loop Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-23 Zhimin Miao, Zhou Sha, Jianzhong He, Yongkai Liang, Lihua Tan, Yuxin Zhao, Xiaobing Cui, Jinmiao Zhong, Ruting Zhong, Huijun Liang, Wendi Yue, Boyang Qiu, Yunzhen Gao, Lan Zhang, Zixin Teng, Zeen He, Li Chen, Rufei Xiao, Xiaofeng Pei, Chengwei He
The therapeutic efficacy of osimertinib (OSI) in EGFR-mutant lung cancer is ultimately limited by the onset of acquired resistance, of which the mechanisms remain poorly understood. Here, we identify a novel long non-coding RNA, LRTOR, as a key driver of OSI resistance in non-small cell lung cancer (NSCLC). Clinical data indicate that elevated LRTOR expression correlates with poor prognosis in OSI-resistant
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Metabolic reprogramming in polycystic kidney disease and other renal ciliopathies. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-22 Sara Clerici,Alessandra Boletta
Primary cilia are solitary organelles formed by a microtubule-based skeleton protruding in a single copy on the surface of most cells. Alterations in their function cause a plethora of human conditions collectively called the ciliopathies. The kidney is frequently and severely affected in the ciliopathies, presenting with a spectrum of phenotypes. Cyst formation is a common trait of all renal ciliopathies
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Lactylation in cancer progression and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-21 Yuxiu Sun, He Wang, Zhe Cui, Tingting Yu, Yuanming Song, Haolai Gao, Ruihong Tang, Xinlei Wang, Binru Li, Wenxin Li, Zhe Wang
Lactate plays a crucial role as an energy substrate, metabolite, and signaling molecule in cancer. Lactate has long been considered a byproduct of glycolysis. Still, the lactate shuttle hypothesis has changed the lactate paradigm, revealing the implications of lactate in cellular metabolism and cellular communications that can transcend the compartment barrier and occur within and between different
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PARP inhibition elicits NK cell-associated immune evasion via potentiating HLA-G expression in tumor Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-19 Siyuan Wang, Yu Xia, Yiyu Qian, Wen Pan, Pu Huang, Ning Jin, Xin Li, Cheng Xu, Dan Liu, Guangnian Zhao, Yong Fang, Christophe Nicot, Qinglei Gao
Resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) poses a significant challenge to enhancing the efficacy of cancer treatments. Beyond the cellular mechanisms intrinsic to tumor cells, the modulation of the tumor immune microenvironment is crucial in dictating the responsiveness to pharmacological interventions. Thus, there is a pressing need to elucidate the intricate interplay between
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MVP-LCN2 axis triggers evasion of ferroptosis to drive hepatocarcinogenesis and sorafenib resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-17 Jiawen Xu, Bo Wang, Qiaoyu Liu, Sheng Guo, Chen Chen, Jun Wu, Xiaoya Zhao, Mengmeng Li, Zhuang Ma, Shimeng Zhou, Yun Qian, Yijin Huang, Zhangding Wang, Chuanjun Shu, Qingxiang Xu, Jingjing Ben, Qiang Wang, Shouyu Wang
RNA-binding proteins (RBPs) are critical regulators in tumorigenesis and therapy resistance by modulating RNA metabolism. However, the role of RBPs in hepatocarcinogenesis and progression remains elusive. Here, RBPs screening and integrating analyses identify major vault protein (MVP) as an oncogenic RBP in the occurrence of hepatocellular carcinoma (HCC) and sorafenib resistance via suppressing ferroptosis
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SOX9-dependent fibrosis drives renal function in nephronophthisis. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-10 Maulin Mukeshchandra Patel,Vasileios Gerakopoulos,Bryan Lettenmaier,Eleni Petsouki,Kurt A Zimmerman,John A Sayer,Leonidas Tsiokas
Fibrosis is a key feature of a broad spectrum of cystic kidney diseases, especially autosomal recessive kidney disorders such as nephronophthisis (NPHP). However, its contribution to kidney function decline and the underlying molecular mechanism(s) remains unclear. Here, we show that kidney-specific deletion of Fbxw7, the recognition receptor of the SCFFBW7 E3 ubiquitin ligase, results in a juvenile-adult
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Clinically translatable mitochondrial gene therapy in muscle using tandem mtZFN architecture. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-09 Pavel A Nash,Keira M Turner,Christopher A Powell,Lindsey Van Haute,Pedro Silva-Pinheiro,Felix Bubeck,Ellen Wiedtke,Eloïse Marques,Dylan G Ryan,Dirk Grimm,Payam A Gammage,Michal Minczuk
Mutations in the mitochondrial genome (mtDNA) often lead to clinical pathologies. Mitochondrially-targeted zinc finger nucleases (mtZFNs) have been successful in reducing the levels of mutation-bearing mtDNA both in vivo and in vitro, resulting in a shift in the genetic makeup of affected mitochondria and subsequently to phenotypic rescue. Given the uneven distribution in the mtDNA mutation load across
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A decisive technical leap forward for personalized medicine to treat mitochondrial diseases. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-09 Abi S Ghifari,Martin Ott
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KpnK48 clone driving hypervirulent carbapenem-resistant Escherichia coli epidemics: Insights into its evolutionary trajectory similar to Klebsiella pneumoniae Drug Resist. Updat. (IF 15.8) Pub Date : 2025-04-08 Meng Wang, Longyang Jin, Ruobing Wang, Qi Wang, Shuyi Wang, Xingyu Wu, Chaoqun Yao, Jukka Corander, Hui Wang
Hypervirulent and carbapenem-resistant pathogens posed a significant and growing threat to global public health. This study focused on the rapid spread of a hypervirulent carbapenem-resistant E. coli (hv-CREC) subclone and its genomic resembles with hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP), driven by recombination impacting both chromosomal and plasmid gene content.
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Generalization of neoantigen-based tumor vaccine by delivering peptide-MHC complex via oncolytic virus. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-07 Chenyi Wang,Yingjun Shi,Da Zhang,Yupeng Sun,Junjie Xie,Bingchen Wu,Cuilin Zhang,Xiaolong Liu
Neoantigen vaccine is a promising breakthrough in tumor immunotherapy. However, the application of this highly personalized strategy in the treatment of solid tumors is hindered by several obstacles, including very costly and time-consuming preparation steps, uncertainty in prediction algorithms and tumor heterogeneity. Universalization of neoantigen vaccine is an ideal yet currently unattainable solution
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Getting to the heart of cardiovascular complications associated with inflammatory arthritis. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-03 Hong Shi,Brian H Annex
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Author Correction: Identification of PTGR2 inhibitors as a new therapeutic strategy for diabetes and obesity. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-03 Yi-Cheng Chang,Meng-Lun Hsieh,Hsiao-Lin Lee,Siow-Wey Hee,Chi-Fon Chang,Hsin-Yung Yen,Yi-An Chen,Yet-Ran Chen,Ya-Wen Chou,Fu-An Li,Yi-Yu Ke,Shih-Yi Chen,Ming-Shiu Hung,Alfur Fu-Hsin Hung,Jing-Yong Huang,Chu-Hsuan Chiu,Shih-Yao Lin,Sheue-Fang Shih,Chih-Neng Hsu,Juey-Jen Hwang,Teng-Kuang Yeh,Ting-Jen Rachel Cheng,Karen Chia-Wen Liao,Daniel Laio,Shu-Wha Lin,Tzu-Yu Chen,Chun-Mei Hu,Ulla Vogel,Daniel Saar
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Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-01 Georgina D Barnabas,Tariq A Bhat,Verena Goebeler,Pascal Leclair,Nadine Azzam,Nicole Melong,Colleen Anderson,Alexis Gom,Seohee An,Enes K Ergin,Yaoqing Shen,Agustina Conrrero,Andrew J Mungall,Karen L Mungall,Christopher A Maxwell,Gregor S D Reid,Martin Hirst,Steven Jones,Jennifer A Chan,Donna L Senger,Jason N Berman,Seth J Parker,Jonathan W Bush,Caron Strahlendorf,Rebecca J Deyell,C James Lim,Philipp
Genomics has transformed the diagnostic landscape of pediatric malignancies by identifying and integrating actionable features that refine diagnosis, classification, and treatment. Yet, translating precision oncology data into effective therapies for hard-to-cure childhood, adolescent, and young adult malignancies remains a significant challenge. We present the case for combining proteomics with patient-derived
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Saccharin disrupts bacterial cell envelope stability and interferes with DNA replication dynamics. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-01 Rubén de Dios,Kavita Gadar,Chris R Proctor,Evgenia Maslova,Jie Han,Mohamed A N Soliman,Dominika Krawiel,Emma L Dunbar,Bhupender Singh,Stelinda Peros,Tom Killelea,Anna-Luisa Warnke,Marius M Haugland,Edward L Bolt,Christian S Lentz,Christian J Rudolph,Ronan R McCarthy
Saccharin has been part of the human diet for over 100 years, and there is a comprehensive body of evidence demonstrating that it can influence the gut microbiome, ultimately impacting human health. However, the precise mechanisms through which saccharin can impact bacteria have remained elusive. In this work, we demonstrate that saccharin inhibits cell division, leading to cell filamentation with
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Targeting HPK1 inhibits neutrophil responses to mitigate post-stroke lung and cerebral injuries. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-04-01 Tingting Zhang,Ying Sun,Jing Xia,Hongye Fan,Dingfang Shi,Qian Wu,Ming Huang,Xiao-Yu Hou
Circulating neutrophils are responsible for poor neurological outcomes and have been implicated in respiratory morbidity after acute ischemic stroke (AIS). However, the molecular mechanisms regulating neutrophil responses and their pathological relevance in post-stroke complications remain unclear. In this study, we investigated the involvement of hematopoietic progenitor kinase 1 (HPK1) in neutrophil
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Liver TET1 promotes metabolic dysfunction-associated steatotic liver disease. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-31 Hongze Chen,Muhammad Azhar Nisar,Joud Mulla,Xinjian Li,Kevin Cao,Shaolei Lu,Katsuya Nagaoka,Shang Wu,Peng-Sheng Ting,Tung-Sung Tseng,Hui-Yi Lin,Xiao-Ming Yin,Wenke Feng,Zhijin Wu,Zhixiang Cheng,William Mueller,Amalia Bay,Layla Schechner,Xuewei Bai,Chiung-Kuei Huang
Global hepatic DNA methylation change has been linked to human patients with metabolic dysfunction-associated steatotic liver disease (MASLD). DNA demethylation is regulated by the TET family proteins, whose enzymatic activities require 2-oxoglutarate (2-OG) and iron that both are elevated in human MASLD patients. We aimed to investigate liver TET1 in MASLD progression. Depleting TET1 using two different
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A quiescence-like/TGF-β1-specific CRISPRi screen reveals drug uptake transporters as secondary targets of kinase inhibitors in AML Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-28 Elahe Rahimian, Masoud Koochak, Sofia Traikov, Michael Schroeder, Silke Brilloff, Silvia Schäfer, Vida Kufrin, Sandra Küchler, Alexander Krüger, Peter Mirtschink, Gustavo Baretton, Evelin Schröck, Denis M. Schewe, Claudia R. Ball, Martin Bornhäuser, Hanno Glimm, Marius Bill, Alexander A. Wurm
Relapse in acute myeloid leukemia (AML) is driven by resistant subclones that survive chemotherapy. It is assumed that these resilient leukemic cells can modify their proliferative behavior by entering a quiescent-like state, similar to healthy hematopoietic stem cells (HSCs). These dormant cells can evade the effects of cytostatic drugs that primarily target actively dividing cells. Although quiescence
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Soluble CD27 differentially predicts resistance to anti-PD1 alone but not with anti-CTLA-4 in melanoma. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-27 Ikuan Sam,Nadine Benhamouda,Lucie Biard,Laetitia Da Meda,Kristell Desseaux,Barouyr Baroudjan,Ines Nakouri,Marion Renaud,Aurélie Sadoux,Marina Alkatrib,Jean-François Deleuze,Maxime Battistella,Yimin Shen,Matthieu Resche-Rigon,Samia Mourah,Celeste Lebbe,Eric Tartour
Metastatic melanoma can be treated with anti-PD-1 monotherapy or in combination with anti-CTLA-4 or anti-Lag3. However, combination therapy is associated with a high risk of toxicity. Recently, we reported that high plasma soluble CD27 (sCD27) levels reflect the intratumoral interaction of CD70-CD27 and dysfunctional T cells in the tumor microenvironment of renal cell carcinoma. In this study, we first
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TFE3 fusions drive oxidative metabolism and ferroptosis resistance in translocation renal cell carcinoma. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-27 Alexandra Helleux,Guillaume Davidson,Antonin Lallement,Fatima Al Hourani,Alexandre Haller,Isabelle Michel,Anas Fadloun,Christelle Thibault-Carpentier,Xiaoping Su,Véronique Lindner,Thibault Tricard,Hervé Lang,Nizar M Tannir,Irwin Davidson,Gabriel G Malouf
The oncogenic mechanisms by which TFE3 fusion proteins drive translocation renal cell carcinoma (tRCC) are poorly characterized. Here, we integrated loss and gain of function experiments with multi-omics analyses in tRCC cell lines and patient tumors. High nuclear accumulation of NONO-TFE3 or PRCC-TFE3 fusion proteins promotes their broad binding across the genome at H3K27ac-marked active chromatin
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Selective tubulin-binding drugs induce pericyte phenotype switching and anti-cancer immunity. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-26 Bo He,Kira H Wood,Zhi-Jie Li,Judith A Ermer,Ji Li,Edward R Bastow,Suraj Sakaram,Phillip K Darcy,Lisa J Spalding,Cameron T Redfern,Jordi Canes,Mafalda Oliveira,Aleix Prat,Javier Cortes,Erik W Thompson,Bruce A Littlefield,Andrew Redfern,Ruth Ganss
The intratumoral immune milieu is crucial for the success of anti-cancer immunotherapy. We show here that stromal modulation by the tubulin-binding anti-cancer drugs combretastatin A4 (CA-4) and eribulin improved tumor perfusion and anti-tumor immunity. This was achieved by reverting highly proliferative, angiogenic pericytes into a quiescent, contractile state which durably normalized the vascular
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Beyond mitotic arrest: the diverse effects of microtubule-targeting drugs on tumor vasculature. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-26 April L Risinger
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Modulating CCTG repeat expansion toxicity in DM2 Drosophila model through TDP1 inhibition. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-25 Yingbao Zhu,Shengwei Xiao,Xinxin Guan,Haitao Deng,Liqiang Ai,Kaijing Fan,Jin Xue,Guangxu Li,Xiaoxue Bi,Qiao Xiao,Yuanjiang Huang,Lin Jiang,Wen Huang,Peng Jin,Ranhui Duan
Myotonic dystrophy type 2 (DM2), caused by CCTG repeat expansion, is a common adult-onset disorder characterized by myotonia and progressive muscle degeneration with no effective treatment. Here, we identified Tyrosyl-DNA phosphodiesterase 1 (TDP1) as a novel modifier for DM2 therapeutic intervention through a high-throughput chemical screening of 2160 compounds. Moreover, we detailed how both genetic
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Exploring the potential of lipid elicitors to enhance plant immunity Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-03-24 Gonçalo Laureano, Ana Rita Matos, Andreia Figueiredo
Lipids besides being components of membranes and storage molecules are also involved in signalling processes and have proven to be vital components in plant defence mechanisms. Over the past decades, the intricate lipid-signalling pathways that underlie the establishment of defence responses have been extensively studied. These molecules can act directly as signalling agents in plant defence or serve
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PARP7 as a new target for activating anti-tumor immunity in cancer. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-24 Katerina Popova,Johannes Benedum,Magdalena Engl,Carola Lütgendorf-Caucig,Piero Fossati,Joachim Widder,Klaus Podar,Dea Slade
ADP-ribosyl transferases (ARTs) are a family of enzymes which catalyze the addition of a chain (PARylation) or a single moiety (MARylation) of ADP-ribose to their substrates. PARP7 is a mono-ADP-ribosyl transferase (mono-ART) which has recently gained attention due to its emerging role as a negative regulator of the type I interferon (IFN-I) and nuclear receptor signaling, and due to its aberrant expression
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Targeting cTRIP12 counteracts ferroptosis resistance and augments sensitivity to immunotherapy in pancreatic cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-22 Hongyi Lin, Shuncang Zhu, Yinhao Chen, Jinpeng Lu, Chengke Xie, Chengyu Liao, Xiaoxiao Huang, Ge Li, Yongding Wu, Zhiyuan Li, Jianfei Hu, Xinquan Lin, Yifeng Tian, Qiaowei Li, Zuwei Wang, Shi Chen
Current therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC) have limited efficacy in increasing patient survival rates, largely due to ferroptosis resistance and immunosuppression. The aim of this study is to identify molecular mechanisms associated with ferroptosis resistance and immunosuppression in PDAC tumour cells.
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Targeting NAT10 attenuates homologous recombination via destabilizing DNA:RNA hybrids and overcomes PARP inhibitor resistance in cancers Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-22 Zhu Xu, Mingming Zhu, Longpo Geng, Jun Zhang, Jing Xia, Qiang Wang, Hongda An, Anliang Xia, Yuanyuan Yu, Shihan Liu, Junjie Tong, Wei-Guo Zhu, Yiyang Jiang, Beicheng Sun
RNA metabolism has been extensively studied in DNA double-strand break (DSB) repair. The RNA acetyltransferase N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification in DSB repair remains largely elusive. In this study, we aim to decipher the role for ac4C modification by NAT10 in DSB repair in hepatocellular carcinoma (HCC).
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DNA methylation changes during acute COVID-19 are associated with long-term transcriptional dysregulation in patients' airway epithelial cells. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-21 Marey Messingschlager,Sebastian D Mackowiak,Maria Theresa Voelker,Matthias Bieg,Jennifer Loske,Robert Lorenz Chua,Johannes Liebig,Sören Lukassen,Loreen Thürmann,Anke Seegebarth,Sven Twardziok,Daria Doncevic,Carl Herrmann,Stephan Lorenz,Sven Klages,Fridolin Steinbeis,Martin Witzenrath,Florian Kurth,Christian Conrad,Leif E Sander,Naveed Ishaque,Roland Eils,Irina Lehmann,Sven Laudi,Saskia Trump
Molecular changes underlying the persistent health effects after SARS-CoV-2 infection remain poorly understood. To discern the gene regulatory landscape in the upper respiratory tract of COVID-19 patients, we performed enzymatic DNA methylome and single-cell RNA sequencing in nasal cells of COVID-19 patients (n = 19, scRNA-seq n = 14) and controls (n = 14, scRNA-seq n = 10). In addition, we resampled
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Microbiome-derived secondary bile acids promote repair of colonic mucosa after injury. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-21 Brecht Attema,Folkert Kuipers
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Targeting FKBP51 prevents stress-induced preterm birth. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-17 Ozlem Guzeloglu-Kayisli,Asli Ozmen,Busra Cetinkaya Un,Burak Un,Jacqueline Blas,Isabella Johnson,Andrea Thurman,Mark Walters,David Friend,Umit A Kayisli,Charles J Lockwood
Preterm birth (PTB) is a leading cause of perinatal morbidity and mortality, with maternal stress-related disorders, such as depression and anxiety, linked to idiopathic PTB (iPTB). At the maternal-fetal interface, decidualized stromal cells (DSCs) exclusively express the progesterone receptor (PR) and play pivotal roles in maintaining pregnancy and initiating labor. DSCs also express FKBP51, a protein
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Widespread antibiotic heterotolerance in bacteria remains undetected by resistance assays Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-15 Bram Van den Bergh, Philip Ruelens, Lieze Agten, Laurence Van Moll, Nele Geerts, Laure Verstraete, Sang Nguyen, Linda De Vooght, Natalie Verstraeten, Paul Cos, Jan Michiels
Despite global efforts, antimicrobial resistance persists. Mechanisms like heterotolerance further undermine antibiotic effectiveness. Testing > 1000 clinical strains revealed widespread heterotolerance largely missed by conventional MIC-based diagnostics. Since AMR alone does not predict treatment success, new tests and strategies incorporating tolerance data are urgently needed to significantly improve
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MHC-I upregulation by macbecin II in the solid tumors potentiates the effect of active immunotherapy. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-14 Ravindra Pramod Deshpande,Kerui Wu,Shih-Ying Wu,Abhishek Tyagi,Eleanor C Smith,Jee-Won Kim,Kounosuke Watabe
We aimed to restore MHC-I expression on the surface of solid tumors including breast cancer and melanoma cells to regain sensitivity to immunotherapy and suppress metastatic progression. We screened a natural compound library and identified macbecin II as a reagent that upregulates MHC-I expression and induces antigen-dependent cell death in pre-invasive and invasive breast cancer models. Furthermore
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Immune training enhances anti-viral responses and improves outcomes in Pax5-/+ mice susceptible to chronic infection. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-13 Zhe Lu,Olivia Stencel,Wei Liu,Eleni Vasileiou,Haifeng C Xu,Piyush Pandey,Paweł Stachura,Abdelrahman Elwy,Anastassia Tsombal,Ann-Sophie Mai,Franziska Auer,Mina N F Morcos,Maximilian Seidl,Sarah Koziel,Peter-Martin Bruch,Sascha Dietrich,Sarah Elitzur,Gunther Hartmann,Karl S Lang,Stefan Janssen,Ute Fischer,Sanil Bhatia,Philipp A Lang,Arndt Borkhardt,Julia Hauer,Aleksandra A Pandyra
Viral infections pose a significant global burden. Host susceptibility to pathogens is determined by many factors including genetic variation that can lead to immunodeficient or dysregulated antiviral immune responses. Pax5 heterozygosity (Pax5-/+), resulting in reduced PAX5 levels in mice, mimics germline or somatic PAX5 dysregulation contributing to diseases such as childhood B-cell precursor acute
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Role of the sulfur-containing amino acid-ROS axis in cancer chemotherapeutic drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-12 Bingli Wu, Yinwei Cheng, Liyan Li, Zepeng Du, Qianlou Liu, Xinyue Tan, Xin Li, Guozhi Zhao, Enmin Li
Chemotherapeutic drug resistance remains a major barrier to effective cancer treatment. Drug resistance could be driven in part by adaptive redox remodeling of cancer cells. Paradoxically, drug-resistant malignancies exhibit elevated reactive oxygen species (ROS), as well as amplified antioxidant defenses, which enable cancer cell survival under therapeutic stress. Central to this adaptation is glutathione
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CD105 blockade restores osimertinib sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-12 Manish Thiruvalluvan, Sandrine Billet, Zhenqiu Liu, Joseph Lownik, Barliz Waissengrin, Hyoyoung Kim, Anton L. Villamejor, Larry Milshteyn, Xiamo Li, Matthew Gayhart, Manuel Araña, Kamya Sankar, Edwin M. Posadas, Jean Lopategui, Sungyong You, Karen L. Reckamp, Neil A. Bhowmick
To investigate the role of CD105 in mediating drug resistance to EGFR-targeted therapy in non-small cell lung cancer (NSCLC).
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The PLAAT family as phospholipid-related enzymes Prog. Lipid. Res. (IF 14.0) Pub Date : 2025-03-10 Toru Uyama, Sumire Sasaki, Mohammad Mamun Sikder, Miki Okada-Iwabu, Natsuo Ueda
The phospholipase A and acyltransferase (PLAAT) family is a group of structurally related proteins that are conserved among vertebrates. In humans, the family comprises five members (PLAAT1–5), which share common domain structures, and functions as phospholipase A1/A2 and acyltransferase enzymes. Regarding acyltransferase activities, PLAATs produce N-acyl-phosphatidylethanolamines, which serve as the
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Bile acid 7α-dehydroxylating bacteria accelerate injury-induced mucosal healing in the colon. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-10 Antoine Jalil,Alessia Perino,Yuan Dong,Jéromine Imbach,Colin Volet,Eduard Vico-Oton,Hadrien Demagny,Lucie Plantade,Hector Gallart-Ayala,Julijana Ivanisevic,Rizlan Bernier-Latmani,Siegfried Hapfelmeier,Kristina Schoonjans
Host-microbiome communication is frequently perturbed in gut pathologies due to microbiome dysbiosis, leading to altered production of bacterial metabolites. Among these, 7α-dehydroxylated bile acids are notably diminished in inflammatory bowel disease patients. Herein, we investigated whether restoration of 7α-dehydroxylated bile acids levels by Clostridium scindens, a human-derived 7α-dehydroxylating
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Novel insights into taxane pharmacology: An update on drug resistance mechanisms, immunomodulation and drug delivery strategies Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-08 Giovanni Luca Beretta, Giuliana Cassinelli, Giacomina Rossi, Amalia Azzariti, Iléana Corbeau, Diego Tosi, Paola Perego
Taxanes are effective in several solid tumors. Paclitaxel, the main clinically available taxane, was approved in the early nineties, for the treatment of ovarian cancer and later on, together with the analogs docetaxel and cabazitaxel, for other malignancies. By interfering with microtubule function and impairing the separation of sister cells at mitosis, taxanes act as antimitotic agents, thereby
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Overcoming cancer therapy resistance: From drug innovation to therapeutics Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-08 Jin-Rui Wei, Meng-Yi Lu, Tian-Hua Wei, Joshua S. Fleishman, Hui Yu, Xiao-Li Chen, Xiang-Tu Kong, Shan-Liang Sun, Nian-Guang Li, Ye Yang, Hai-Wen Ni
One of the major limitations of cancer therapy is the emergence of drug resistance. This review amis to provide a focused analysis of the multifactorial mechanisms underlying therapy resistance,with an emphasis on actionable insights for developing novel therapeutic strategies. It concisely outlines key factors contributing to therapy resistance, including drug delivery barriers, cancer stem cells
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TGFβ-activated Asporin interacts with STMN1 to promote prostate cancer docetaxel chemoresistance and metastasis by upregulating the Wnt/β-catenin signaling pathway Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-08 Shengdong Ge, Jinpeng Cen, Xiaofeng Liu, Yaying Hong, Yuting Tang, Yuzhong Yu, Haolin Li, Tao Xie, Chong Wang, Maoping Cai, Yang Qiu, Xianzi Zeng, Tianming Peng, Qu Li, Qianyi Li, Xingcheng Wu, Xian-Lu Song, Shan-Chao Zhao
Prostate cancer (PCa) remains a significant challenge in oncology due to high rates of drug resistance following standard treatment with docetaxel-based chemotherapy. Asporin (ASPN) has been regarded as an oncogene and its upregulation is closely associated with malignant behavior and poor prognosis in multiple cancers. Studies indicated that abnormal activation of the Wnt/β-catenin signaling pathway
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Aging and senescence: Key players in brain tumor progression and drug resistance Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-08 Chao Zhang, Neha, Jiaqi Zhang, Prashant Dhaha, Xiaodie Li, Sarad Kumar Mishra, Joshua Fleishman, Suhel Parvez, Saurabh Kumar Jha, Min Huang
Aging plays a critical role in the development, progression, and therapeutic challenges associated with brain tumors, particularly glioblastomas (GBM). As the population ages, the incidence of brain tumors, including GBM, increases, with aging emerging as a significant prognostic factor influencing survival outcomes. This review examines the molecular mechanisms linking aging and brain tumor progression
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Chaperone-mediated autophagy regulates the metastatic state of mesenchymal tumors. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-07 Xun Zhou,Eva Berenger,Yong Shi,Vera Shirokova,Elena Kochetkova,Tina Becirovic,Boxi Zhang,Vitaliy O Kaminskyy,Yashar Esmaeilian,Kayoko Hosaka,Cecilia Lindskog,Per Hydbring,Simon Ekman,Yihai Cao,Maria Genander,Marcin Iwanicki,Erik Norberg,Helin Vakifahmetoglu-Norberg
Tumors often recapitulate programs to acquire invasive and dissemination abilities, during which pro-metastatic proteins are distinctively stabilized in cancer cells to drive further progression. Whether failed protein degradation affects the metastatic programs of cancer remains unknown. Here, we show that the human cancer cell-specific knockout (KO) of LAMP-2A, a limiting protein for chaperone-mediated
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Methotrexate resistance and its regulatory mechanisms in pediatric tumors and beyond Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-05 Jing Nie, Lantian Huang, Yan Shen, Hongai Pan, Siwan Wang, Huawei Zhao, Peng Gao, Jufei Yang, Xiaojun Huang, Su Zeng, Jing Miao
Methotrexate (MTX) is a critical antimetabolite drug in treating various pediatric diseases, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), brain tumors, osteosarcoma, inflammatory myofibroblastic tumor (IMT), juvenile scleroderma (JS), and juvenile idiopathic arthritis (JIA). MTX acts as a folate antagonist by inhibiting dihydrofolate reductase (DHFR), an enzyme essential
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Precise mycobacterial species and subspecies identification using the PEP-TORCH peptidome algorithm. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-03-04 Duran Bao,Sudipa Maity,Lingpeng Zhan,Seungyeon Seo,Qingbo Shu,Christopher J Lyon,Bo Ning,Adrian Zelazny,Tony Y Hu,Jia Fan
Mycobacterial infections pose a significant global health concern, requiring precise identification for effective treatment. However, diagnosing them is challenging due to inaccurate identifications and prolonged times. In this study, we aimed to develop a novel peptidome-based method using mycobacterial growth indicator tube (MGIT) cultures for faster and more accurate identification. We created the
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Targeting TRAP1-dependent metabolic reprogramming to overcome doxorubicin resistance in quiescent breast cancer Drug Resist. Updat. (IF 15.8) Pub Date : 2025-03-03 Muhammad Zubair Saleem, Ruyi Huang, Yingying Huang, Xin Guo, Yang Liu, Miao Gao, Yinjuan Fan, Zhe-Sheng Chen, Zun-Fu Ke, Shengnan Ye, Jianhua Xu
TRAP1 is involved in metabolic reprogramming and promotes drug resistance. We aimed to explore whether a novel HSP90 inhibitor, C210, overcomes doxorubicin (DOX) resistance of quiescent breast cancer cells by targeting TRAP1.
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DTX2 attenuates Lenvatinib-induced ferroptosis by suppressing docosahexaenoic acid biosynthesis through HSD17B4-dependent peroxisomal β-oxidation in hepatocellular carcinoma Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-28 Zhongyan Zhang, Qi Zhou, Zhenchong Li, Fuxin Huang, Ke Mo, Cheng Shen, Xing Niu, Baohua Hou, Chuanzhao Zhang, Shanzhou Huang
Emerging resistance to Lenvatinib, which is used as a first-line agent for the treatment of advanced hepatocellular carcinoma (HCC), is still a concern. The aim of this study was to determine core factors of Lenvatinib resistance (LR) and their underlying molecular mechanisms.
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The combination of flaxseed lignans and PD-1/ PD-L1 inhibitor inhibits breast cancer growth via modulating gut microbiome and host immunity Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-28 Hao Wu, Jiena Liu, Xing-Hua Zhang, Shengye Jin, Ping Li, Huidi Liu, Liuying Zhao, Jianyu Wang, Shilu Zhao, Hong-Da Tian, Jin-Ru Lai, Yi Hao, Gui-Rong Liu, Kaijian Hou, Meisi Yan, Shu-Lin Liu, Da Pang
Patients with breast cancer (BC) who benefit from the PD-1/PD-L1 inhibitor (PDi) is limited, necessitating novel strategies to improve immunotherapy efficacy of BC. Here we aimed to investigate the inhibitory effects of flaxseed lignans (FL) on the biological behaviors of BC and evaluate the roles of FL in enhancing the anticancer effects of PDi.
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Deubiquitination of RIPK3 by OTUB2 potentiates neuronal necroptosis after ischemic stroke. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-28 Fuqi Mei,Deyu Deng,Zijun Cao,Liyan Lou,Kangmin Chen,Minjie Hu,Zhenhu Zhu,Jiangyun Shen,Jianzhao Zhang,Jie Liang,Jingyong Huang,Min Bao,Ari Waisman,Xu Wang
As a common and severe cerebrovascular disease, ischemic stroke casts a significant shadow over global health. Unfortunately, the mechanisms regulating neuronal death in the affected areas remain largely unclear. Here, we found that deletion of the deubiquitinating enzyme Otubain-2 (OTUB2) significantly alleviated ischemia-induced cerebral infarction and neurological deficits, accompanied by a reduction
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Safe CAR-T: shedding light on CAR-related T-cell malignancies. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-28 Qibin Liao,Jianqing Xu
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Resistance to immunotherapy in non-small cell lung cancer: Unraveling causes, developing effective strategies, and exploring potential breakthroughs Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-25 Shuang Dong, Xiaoyu Li, Qing Huang, Yuanxiang Li, Jinjiao Li, Xianmin Zhu, Chang Xue, Runzhi Chen, Yuan Zeng, Jingyi Wu, Yi Zhong, Sheng Hu
Over the last two decades, advancements in deciphering the intricate interactions between oncology and immunity have fueled a meteoric rise in immunotherapy for non-small cell lung cancer, typified by an explosive growth of immune checkpoint inhibitors. However, resistance to immunotherapy remains inevitable. Herein we unravel the labyrinthine mechanisms of resistance to immunotherapy, characterized
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Pertussis before, during and after Covid-19. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-24 Camille Locht
After the Covid-19 pandemic, pertussis has made a spectacular comeback in Europe and many other parts of the world, while during the pandemic it had essentially disappeared because of the social distancing requirements. However, even before the Covid-19 pandemic, the disease was on the rise in many countries, especially those that have replaced whole-cell pertussis vaccines by acellular pertussis vaccines
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X-linked myopathy with excessive autophagy: characterization and therapy testing in a zebrafish model. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-24 Lily Huang,Rebecca Simonian,Michael A Lopez,Muthukumar Karuppasamy,Veronica M Sanders,Katherine G English,Lacramioara Fabian,Matthew S Alexander,James J Dowling
X-linked myopathy with excessive autophagy (XMEA), a rare childhood-onset autophagic vacuolar myopathy caused by mutations in VMA21, is characterized by proximal muscle weakness and progressive vacuolation. VMA21 encodes a protein chaperone of the vacuolar hydrogen ion ATPase, the loss of which leads to lysosomal neutralization and impaired function. At present, there is an incomplete understanding
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Centromere protein U mediates the ubiquitination and degradation of RPS3 to facilitate temozolomide resistance in glioblastoma Drug Resist. Updat. (IF 15.8) Pub Date : 2025-02-21 Jinmin Sun, Wenyu Zhao, Lei Zhang, Sicheng Wu, Senrui Xue, Haowei Cao, Biao Xu, Xinmiao Li, Nan Hu, Tao Jiang, Yixin Xu, Zhifei Wang, Chao Zhang, Jing Ren
Temozolomide (TMZ) is the first-line chemotherapeutic agent for glioblastoma (GBM) therapy; however, resistance to TMZ remains a major obstacle in GBM treatment. The aim of this study is to elucidate the mechanisms underlying TMZ resistance and explore how to enhance the sensitivity of GBM to TMZ.
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Lanatoside C activates the E3 ligase STUB1 to inhibit FOXP3 transcriptional activity and promote antitumor immunity. EMBO Mol. Med. (IF 9.0) Pub Date : 2025-02-20 Qian Zhou,Tong Yang,Xixi Yu,Bo Li,Jin Liu,Yongxin Mao,Rongxiang Guo,Zhuo Feng,Li Zhou,Guandi Zeng,Nan Li,Jinxia Liang,Lu Liu,Pengju Feng,Hong-Bing Shu,Liang Chen
Regulatory T cells (Tregs) play critical roles in inhibiting antitumor immunity, which is dependent on FOXP3-mediated transcriptional activity. However, no Treg-specific therapeutics has been approved for clinical use. We performed a high-throughput screen of FDA-approved drugs for potential inhibitors of FOXP3 transcriptional activity. These efforts identified Lanatoside C (Lac), which potently inhibits