Pub Date : 2025-07-17DOI: 10.1016/j.chembiol.2025.06.007
Zeba Rizvi , Gabriel C. Lander
The E3 ligase complex SIFI silences the integrated stress response (ISR) by targeting stress-induced proteins for degradation. In the May 6th issue of Nature, Yang et al.1 revealed how this megadalton complex recognizes diverse substrates and coordinates ubiquitin chain formation. Their insights into the ISR shutdown mechanism suggest new avenues for modulating stress responses in neurodegenerative disease.
{"title":"Silencing stress: Structural insights into ISR termination by the SIFI ubiquitin ligase","authors":"Zeba Rizvi , Gabriel C. Lander","doi":"10.1016/j.chembiol.2025.06.007","DOIUrl":"10.1016/j.chembiol.2025.06.007","url":null,"abstract":"<div><div>The E3 ligase complex SIFI silences the integrated stress response (ISR) by targeting stress-induced proteins for degradation. In the May 6<sup>th</sup> issue of <em>Nature</em>, Yang et al.<span><span><sup>1</sup></span></span> revealed how this megadalton complex recognizes diverse substrates and coordinates ubiquitin chain formation. Their insights into the ISR shutdown mechanism suggest new avenues for modulating stress responses in neurodegenerative disease.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 7","pages":"Pages 905-907"},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-17DOI: 10.1016/j.chembiol.2025.06.003
Flore Nardella , Tiantian Jiang , Lushun Wang , Monica J. Bohmer , Subhoja Chakraborty , John Okombo , Jaeson Calla , Tatiane Macedo Silva , Samuel Pazicky , Jianwei Che , Jin Jeon , Evie Vincent , Nonlawat Boonyalai , Rachael Coyle , Mairi J. Buchanan , Samuel Schaefer , Daisy Chen , Amaan Khan , Emily Mayville , Mariana Laureano De Souza , Debopam Chakrabarti
Kinase inhibitors are potent therapeutics, but most essential Plasmodium kinases remain unexploited as antimalarial targets. We identified compound 12, a type II kinase inhibitor based on aminopyridine and 2,6-benzimidazole scaffolds, as a lead compound with nanomolar potency, fast action, and in vivo activity in the Plasmodium berghei rodent malaria model. Three-hybrid luciferase fragment complementation, enzymatic studies, and cellular thermal shift assays implicated Plasmodium protein kinase 6 (PfPK6) as the target. However, conditional knockdown of PfPK6 did not alter 12 potency, suggesting complex mechanisms of action. In vitro selection for compound 12 resistance revealed mutations in three transporters: multidrug-resistance protein 1, chloroquine resistance transporter and V-type ATPase, indicating a digestive vacuole site of action. Compound 12 inhibited β-hematin and hemozoin formation while increasing free heme levels, suggesting antimalarial activity via blockade of heme detoxification. Our studies repurpose a safe human kinase inhibitor as a potent, fast-acting antimalarial with established in vivo efficacy.
{"title":"Plasmodium falciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity","authors":"Flore Nardella , Tiantian Jiang , Lushun Wang , Monica J. Bohmer , Subhoja Chakraborty , John Okombo , Jaeson Calla , Tatiane Macedo Silva , Samuel Pazicky , Jianwei Che , Jin Jeon , Evie Vincent , Nonlawat Boonyalai , Rachael Coyle , Mairi J. Buchanan , Samuel Schaefer , Daisy Chen , Amaan Khan , Emily Mayville , Mariana Laureano De Souza , Debopam Chakrabarti","doi":"10.1016/j.chembiol.2025.06.003","DOIUrl":"10.1016/j.chembiol.2025.06.003","url":null,"abstract":"<div><div>Kinase inhibitors are potent therapeutics, but most essential <em>Plasmodium</em> kinases remain unexploited as antimalarial targets. We identified compound <strong>12</strong>, a type II kinase inhibitor based on aminopyridine and 2,6-benzimidazole scaffolds, as a lead compound with nanomolar potency, fast action, and <em>in vivo</em> activity in the <em>Plasmodium berghei</em> rodent malaria model. Three-hybrid luciferase fragment complementation, enzymatic studies, and cellular thermal shift assays implicated <em>Plasmodium</em> protein kinase 6 (PfPK6) as the target. However, conditional knockdown of PfPK6 did not alter <strong>12</strong> potency, suggesting complex mechanisms of action. <em>In vitro</em> selection for compound <strong>12</strong> resistance revealed mutations in three transporters: multidrug-resistance protein 1, chloroquine resistance transporter and V-type ATPase, indicating a digestive vacuole site of action. Compound <strong>12</strong> inhibited β-hematin and hemozoin formation while increasing free heme levels, suggesting antimalarial activity via blockade of heme detoxification. Our studies repurpose a safe human kinase inhibitor as a potent, fast-acting antimalarial with established <em>in vivo</em> efficacy.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 7","pages":"Pages 926-941.e23"},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-17DOI: 10.1016/j.chembiol.2025.06.004
Maoyuan Linghu , Xianyu Luo , Xinru Zhou , Didi Liu , Qian Huang , Yi Ru , Yingli Luo , Yinchu Ma , Yi Huang
Ferroptosis, a form of regulated cell death, is characterized by iron-dependent phospholipid peroxidation and is closely linked to various liver diseases. Although covalent inhibitors have gained attention for their high potency and prolonged effects, no specific covalent inhibitor for ferroptosis exists. Here, we identify Rociletinib (ROC) as a potent inhibitor of ferroptosis through virtual screening and mechanistic studies. Our results demonstrate that ROC covalently binds to cysteine 170 of ACSL4, inhibiting its enzymatic activity and thereby suppressing lipid peroxidation and ferroptosis. ROC effectively mitigates ferroptosis-mediated acute liver injury in mouse models. These findings establish ROC as the targeted covalent inhibitor directly targeting ACSL4, offering a promising therapeutic strategy for ferroptosis-related diseases.
{"title":"Covalent inhibition of ACSL4 alleviates ferroptosis-induced acute liver injury","authors":"Maoyuan Linghu , Xianyu Luo , Xinru Zhou , Didi Liu , Qian Huang , Yi Ru , Yingli Luo , Yinchu Ma , Yi Huang","doi":"10.1016/j.chembiol.2025.06.004","DOIUrl":"10.1016/j.chembiol.2025.06.004","url":null,"abstract":"<div><div>Ferroptosis, a form of regulated cell death, is characterized by iron-dependent phospholipid peroxidation and is closely linked to various liver diseases. Although covalent inhibitors have gained attention for their high potency and prolonged effects, no specific covalent inhibitor for ferroptosis exists. Here, we identify Rociletinib (ROC) as a potent inhibitor of ferroptosis through virtual screening and mechanistic studies. Our results demonstrate that ROC covalently binds to cysteine 170 of ACSL4, inhibiting its enzymatic activity and thereby suppressing lipid peroxidation and ferroptosis. ROC effectively mitigates ferroptosis-mediated acute liver injury in mouse models. These findings establish ROC as the targeted covalent inhibitor directly targeting ACSL4, offering a promising therapeutic strategy for ferroptosis-related diseases.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 7","pages":"Pages 942-954.e5"},"PeriodicalIF":6.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.011
Nil Casajuana-Martin , Eli F. McDonald , M. Madan Babu
G protein-coupled receptors (GPCRs) are increasingly recognized as part of interconnected, cell-context-specific signaling networks. In the June 5th issue of Molecular Cell, Dehkhoda et al.1 demonstrate that the constitutive activity of the ghrelin receptor drives dopamine D2 receptor-dependent calcium mobilization, highlighting the complexity of GPCR signaling and opening new avenues for therapeutic development.
{"title":"Flush with insight: Decoding GPCR crosstalk in the spinal defecation center","authors":"Nil Casajuana-Martin , Eli F. McDonald , M. Madan Babu","doi":"10.1016/j.chembiol.2025.05.011","DOIUrl":"10.1016/j.chembiol.2025.05.011","url":null,"abstract":"<div><div>G protein-coupled receptors (GPCRs) are increasingly recognized as part of interconnected, cell-context-specific signaling networks. In the June 5<sup>th</sup> issue of <em>Molecular Cell</em>, Dehkhoda et al.<span><span><sup>1</sup></span></span> demonstrate that the constitutive activity of the ghrelin receptor drives dopamine D2 receptor-dependent calcium mobilization, highlighting the complexity of GPCR signaling and opening new avenues for therapeutic development.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 786-788"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.002
Jie Liu , Yuandong Liu , Dongmin Yin , Yang Tian
Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of ∼60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds. More importantly, protein engineering of residue mutation and linker peptides flexibility expanded linear range from 10 μM to 6 mM, accelerated on/off times down to 35/40 ms. This toolkit realized real-time quantifying of Glu both at edge of cleft and peri-soma, we discovered that Glu was almost released through SLC7A11 channels in calyx of held synapse upon oxygen-glucose-deprivation, while Glu was mainly released through hemichannels upon β-amyloid42 stimulation. Our work provided a methodology for investigating Glu release and reuptake and offered insights for Glu related pathology.
{"title":"Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma","authors":"Jie Liu , Yuandong Liu , Dongmin Yin , Yang Tian","doi":"10.1016/j.chembiol.2025.05.002","DOIUrl":"10.1016/j.chembiol.2025.05.002","url":null,"abstract":"<div><div>Simultaneously monitoring glutamate (Glu) dynamic at edge of synaptic cleft and peri-soma is crucial for understanding Glu-related pathology. Here, we created an electrochemical Glu sensors toolkit with spatial resolution of ∼60 nm, combining biologically engineered Glu binding protein for specifically capturing Glu together with chemically designed ferrocene groups for signal labeling. Modulation conjugation approach between GluR and ferrocene significantly improved sensitivity up to 32-folds. More importantly, protein engineering of residue mutation and linker peptides flexibility expanded linear range from 10 μM to 6 mM, accelerated on/off times down to 35/40 ms. This toolkit realized real-time quantifying of Glu both at edge of cleft and peri-soma, we discovered that Glu was almost released through SLC7A11 channels in calyx of held synapse upon oxygen-glucose-deprivation, while Glu was mainly released through hemichannels upon β-amyloid<sub>42</sub> stimulation. Our work provided a methodology for investigating Glu release and reuptake and offered insights for Glu related pathology.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 885-898.e11"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144202419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.005
Marta Baro , Hojin Lee , Vanessa Kelley , Rongliang Lou , Chatchai Phoomak , Katerina Politi , Caroline J. Zeiss , Michael Van Zandt , Joseph N. Contessa
Protein asparagine (N)-glycosylation, which promotes the folding and trafficking of cell surface receptors, has not traditionally been viewed as a viable target in oncology due to the essential and non-redundant enzymatic activities required for glycan synthesis and transfer. However, in mammals, an exception is the presence of the oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A and STT3B. In this study, we investigate the biological activity of OST inhibitors and develop a strategy for selectively inhibiting N-glycosylation that is optimized for its downstream effects on the EGFR glycoprotein. Small molecules with improved pharmacokinetic properties and selective preferences for STT3A or STT3B were synthesized, characterized in vitro, and advanced to in vivo testing. The lead compound from this series, NGI-189, induces tumor regression or growth delay in patient-derived and TKI-resistant EGFR-mutant lung cancer xenografts without causing toxicity. Collectively, these findings suggest that bioavailable OST inhibitors can be developed as therapeutic agents for oncology.
{"title":"Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation","authors":"Marta Baro , Hojin Lee , Vanessa Kelley , Rongliang Lou , Chatchai Phoomak , Katerina Politi , Caroline J. Zeiss , Michael Van Zandt , Joseph N. Contessa","doi":"10.1016/j.chembiol.2025.05.005","DOIUrl":"10.1016/j.chembiol.2025.05.005","url":null,"abstract":"<div><div>Protein asparagine (N)-glycosylation, which promotes the folding and trafficking of cell surface receptors, has not traditionally been viewed as a viable target in oncology due to the essential and non-redundant enzymatic activities required for glycan synthesis and transfer. However, in mammals, an exception is the presence of the oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A and STT3B. In this study, we investigate the biological activity of OST inhibitors and develop a strategy for selectively inhibiting N-glycosylation that is optimized for its downstream effects on the EGFR glycoprotein. Small molecules with improved pharmacokinetic properties and selective preferences for STT3A or STT3B were synthesized, characterized <em>in vitro</em>, and advanced to <em>in vivo</em> testing. The lead compound from this series, NGI-189, induces tumor regression or growth delay in patient-derived and TKI-resistant EGFR-mutant lung cancer xenografts without causing toxicity. Collectively, these findings suggest that bioavailable OST inhibitors can be developed as therapeutic agents for oncology.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 839-853.e6"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.007
Yuchen Zhang (章雨辰) , Hongpeng Li (李鸿鹏) , Yi Hao (郝熠) , Jiaqi Chen (陈家祺) , Xing Chen (陈兴) , Hang Yin (尹航)
Tumor associated macrophages (TAMs) exhibit a high capacity to take up glucose. However, how metabolic cues derived from glucose rewire TAMs remains unclear. Here, we report that glucose metabolism-driven protein O-GlcNAcylation increases in TAMs and shapes the differentiation and protumoral function of TAMs. Deficiency of O-GlcNAc transferase (OGT) in TAMs restricted tumor growth by reducing the proportion of C1QC+ F4/80+ TREM2+ MerTK+ TAMs as well as Trem2 expression, which in turn preserved the cytotoxic function of effector CD8+ T cells while exhibiting reduced features of exhaustion. Mechanistically, O-GlcNAc targeted the macrophage-specific transcription factor EGR2 to promote its transcriptional activity. Transcriptional profiling revealed that OGT increased EGR2-related motifs accessibility in TAMs. O-GlcNAcylation of EGR2 at serine 299 enhanced its binding to myeloid cell differentiation-associated genes, including Trem2, thus facilitating the protumoral function of TAMs in GM-CSF-sufficient tumor. Overall, our work defines a tumor-specific reprogramming of protumoral TAMs via O-GlcNAc-modified EGR2 transcriptional regulation.
{"title":"EGR2 O-GlcNAcylation orchestrates the development of protumoral macrophages to limit CD8+ T cell antitumor responses","authors":"Yuchen Zhang (章雨辰) , Hongpeng Li (李鸿鹏) , Yi Hao (郝熠) , Jiaqi Chen (陈家祺) , Xing Chen (陈兴) , Hang Yin (尹航)","doi":"10.1016/j.chembiol.2025.05.007","DOIUrl":"10.1016/j.chembiol.2025.05.007","url":null,"abstract":"<div><div>Tumor associated macrophages (TAMs) exhibit a high capacity to take up glucose. However, how metabolic cues derived from glucose rewire TAMs remains unclear. Here, we report that glucose metabolism-driven protein O-GlcNAcylation increases in TAMs and shapes the differentiation and protumoral function of TAMs. Deficiency of O-GlcNAc transferase (OGT) in TAMs restricted tumor growth by reducing the proportion of C1QC<sup>+</sup> F4/80<sup>+</sup> TREM2<sup>+</sup> MerTK<sup>+</sup> TAMs as well as <em>Trem2 e</em>xpression, which in turn preserved the cytotoxic function of effector CD8<sup>+</sup> T cells while exhibiting reduced features of exhaustion. Mechanistically, O-GlcNAc targeted the macrophage-specific transcription factor EGR2 to promote its transcriptional activity. Transcriptional profiling revealed that OGT increased EGR2-related motifs accessibility in TAMs. O-GlcNAcylation of EGR2 at serine 299 enhanced its binding to myeloid cell differentiation-associated genes, including <em>Trem2</em>, thus facilitating the protumoral function of TAMs in GM-CSF-sufficient tumor. Overall, our work defines a tumor-specific reprogramming of protumoral TAMs via O-GlcNAc-modified EGR2 transcriptional regulation.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 809-825.e7"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.004
Yongliang Liu , Hui Hua , Yalan Cao , Minjing Li , Hongying Zhang , Shan Du , Jieya Liu , Ting Luo , Yangfu Jiang
Inositol-requiring enzyme 1α (IRE1α) signaling is one of three arms of the unfolded protein response, playing a vital role in maintaining endoplasmic reticulum homeostasis. Pharmacological modulation of this pathway offers potential therapeutic strategies for various diseases. Molecular glues may regulate protein stability and activity by inducing protein-protein interaction. Here, we find that verteporfin functions as a molecular glue, promoting IRE1α dimerization and activation. Specifically, verteporfin binds to IRE1α, facilitating its dimerization, which relies on the His692 residue. This activation of IRE1α triggers XBP1 splicing and miR-153-mediated downregulation of PTEN, along with AKT phosphorylation. Additionally, we identify the pro-metastasis gene BACH1 as a novel target of miR-153, which is downregulated by IRE1α and verteporfin. While verteporfin inhibits breast cancer cell viability and invasion, its combination with an AKT inhibitor synergistically suppresses breast cancer progression. Our findings establish a mechanistic link between IRE1α and PI3K/AKT signaling, highlighting a possibility for therapeutic intervention.
{"title":"Mechanism by which the molecular glue-like verteporfin induces IRE1α dimerization and activation to synergize with AKT inhibition in breast cancer","authors":"Yongliang Liu , Hui Hua , Yalan Cao , Minjing Li , Hongying Zhang , Shan Du , Jieya Liu , Ting Luo , Yangfu Jiang","doi":"10.1016/j.chembiol.2025.05.004","DOIUrl":"10.1016/j.chembiol.2025.05.004","url":null,"abstract":"<div><div>Inositol-requiring enzyme 1α (IRE1α) signaling is one of three arms of the unfolded protein response, playing a vital role in maintaining endoplasmic reticulum homeostasis. Pharmacological modulation of this pathway offers potential therapeutic strategies for various diseases. Molecular glues may regulate protein stability and activity by inducing protein-protein interaction. Here, we find that verteporfin functions as a molecular glue, promoting IRE1α dimerization and activation. Specifically, verteporfin binds to IRE1α, facilitating its dimerization, which relies on the His692 residue. This activation of IRE1α triggers XBP1 splicing and miR-153-mediated downregulation of PTEN, along with AKT phosphorylation. Additionally, we identify the pro-metastasis gene <em>BACH1</em> as a novel target of miR-153, which is downregulated by IRE1α and verteporfin. While verteporfin inhibits breast cancer cell viability and invasion, its combination with an AKT inhibitor synergistically suppresses breast cancer progression. Our findings establish a mechanistic link between IRE1α and PI3K/AKT signaling, highlighting a possibility for therapeutic intervention.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 854-871.e6"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144211168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.010
Emre Pekbilir , Dorothee Dormann
In the June 5th issue of Molecular Cell, Das et al.1 quantified the stability of condensates and fibrils formed from the prion-like low complexity region of hnRNPA1. They demonstrate that condensate interiors function as sinks and suppress fibril growth by slowing protein efflux, illuminating the interplay between condensation and fibril formation.
{"title":"Two sides of a co(i)ndensate","authors":"Emre Pekbilir , Dorothee Dormann","doi":"10.1016/j.chembiol.2025.05.010","DOIUrl":"10.1016/j.chembiol.2025.05.010","url":null,"abstract":"<div><div>In the June 5<sup>th</sup> issue of <em>Molecular Cell</em>, Das et al.<span><span><sup>1</sup></span></span> quantified the stability of condensates and fibrils formed from the prion-like low complexity region of hnRNPA1. They demonstrate that condensate interiors function as sinks and suppress fibril growth by slowing protein efflux, illuminating the interplay between condensation and fibril formation.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 783-785"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-06-19DOI: 10.1016/j.chembiol.2025.05.006
Rodion Gordzevich , Eric D. Brown
Antimalarial drug discovery largely relies on nutrient-rich media that may obscure physiologically relevant targets. In this issue of Cell Chemical Biology, Molina et al.1 validate the plasmodial surface anion channel as essential for Plasmodium falciparum survival under nutrient-restricted conditions, demonstrating how physiological media can expose druggable biology overlooked by standard screening approaches.
{"title":"Host-like conditions validate nutrient transport as an antimalarial drug target","authors":"Rodion Gordzevich , Eric D. Brown","doi":"10.1016/j.chembiol.2025.05.006","DOIUrl":"10.1016/j.chembiol.2025.05.006","url":null,"abstract":"<div><div>Antimalarial drug discovery largely relies on nutrient-rich media that may obscure physiologically relevant targets. In this issue of <em>Cell Chemical Biology</em>, Molina et al.<span><span><sup>1</sup></span></span> validate the plasmodial surface anion channel as essential for <em>Plasmodium falciparum</em> survival under nutrient-restricted conditions, demonstrating how physiological media can expose druggable biology overlooked by standard screening approaches.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"32 6","pages":"Pages 777-779"},"PeriodicalIF":6.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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