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Cell Chemical Biology

@cp-cellchembiol.bsky.social

Cell Chemical Biology is a #chemicalbiology journal from @cellpress.bsky.social. Editor-in-Chief @mishtudey.bsky.social

5,847 Followers  |  106 Following  |  485 Posts  |  Joined: 13.12.2023  |  1.5502

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Site-resolved assessment of targeted protein degradation Moreno Ballesteros et al. introduce a site-resolved strategy combining genetic code expansion and bioorthogonal chemistry to evaluate how ligand binding sites influence targeted protein degradation. This approach offers a powerful framework to accelerate degrader design, enable target validation, and broadly explore the potential of induced proximity.
18.07.2025 19:30 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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A cereblon-based glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner Sylvain et al. identified NK7-902, a potent NEK7 degrader. While NK7-902 effectively degrades NEK7 in human and murine systems, inhibition of NLRP3 activity varies by context. This study deepens insight into NEK7’s role in the NLRP3 inflammasome and raises questions about the therapeutic potential of NEK7 degraders for NLRP3-driven diseases.
18.07.2025 18:30 β€” πŸ‘ 2    πŸ” 1    πŸ’¬ 0    πŸ“Œ 1
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Covalent inhibition of ACSL4 alleviates ferroptosis-induced acute liver injury Linghu et al. demonstrate that Rociletinib covalently binds to cysteine 170 of ACSL4, inhibiting its activity to suppress lipid peroxidation and ferroptosis, thereby alleviating ferroptosis-mediated acute liver injury in mouse models.
18.07.2025 17:30 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Plasmodium falciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity Nardella et al. repurposed a kinase inhibitor for malaria treatment, addressing the challenge posed by Plasmodium falciparum’s resistance to most existing antimalarial drugs. The inhibitor targets protein kinase 6 and hemozoin formation pathway involved in heme detoxication, highlighting the complexity and potential effectiveness of its antiplasmodial action.
18.07.2025 16:30 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Silencing stress: Structural insights into ISR termination by the SIFI ubiquitin ligase 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. 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.
18.07.2025 15:30 β€” πŸ‘ 5    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
Powering the powerhouse: Mitochondrial NADPH propels oxidative metabolism Mitochondrial NADPH is abundant, but the reason why was uncertain. In a study published in Nature Cell Biology, Kim et al. identified an important role of NADK2-derived mitochondrial NADPH in mitochondrial fatty acid synthesis (mtFAS) through direct quantification of the products built by mtFAS. This work opens the door to understanding how NADK2, mitochondrial NADPH, and mtFAS regulate mitochondrial function.
18.07.2025 14:30 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Ribosomal RNA transcription regulates splicing through ribosomal protein RPL22 Fan et al. uncovered a mechanism linking rRNA synthesis to spliceosomal regulation. Using large-scale cancer cell line screens with specific RNA polymerase I inhibitors, they identified a non-canonical ribotoxic stress pathway mediated by RPL22, RPL22L1, and MDM4, with RPL22 acting as a master splicing regulator coordinated with rRNA synthesis.
18.07.2025 13:30 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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RPL22 links ribosome biogenesis, RNA splicing, and sensitivity to RNA polymerase I inhibition In this issue of Cell Chemical Biology, Fan et al. identify that mutations in the ribosomal protein RPL22 confer sensitivity to RNA polymerase I inhibitors. RPL22 regulates MDM4 function and cell death via splicing of the MDM4 mRNA. These findings connect ribosome biogenesis with RNA splicing through RPL22.
18.07.2025 12:30 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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The July issue of @cp-cellchembiol.bsky.social‬ is live. Read the full issue here: http://dlvr.it/TLzFLF

17.07.2025 19:21 β€” πŸ‘ 4    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Attend the 2025 Bringing Chemistry to Medicine Symposium to learn from leading experts in transcription, chromatin regulation, computational biology and chemical biology. Registration is free and available both in-person and virtually.

14.07.2025 16:00 β€” πŸ‘ 5    πŸ” 5    πŸ’¬ 1    πŸ“Œ 0
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A cereblon-based glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner Sylvain et al. identified NK7-902, a potent NEK7 degrader. While NK7-902 effectively degrades NEK7 in human and murine systems, inhibition of NLRP3 activity varies by context. This study deepens insight into NEK7’s role in the NLRP3 inflammasome and raises questions about the therapeutic potential of NEK7 degraders for NLRP3-driven diseases.

Online now! #chembiol

14.07.2025 15:30 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
Preview
Covalent inhibition of ACSL4 alleviates ferroptosis-induced acute liver injury Linghu et al. demonstrate that Rociletinib covalently binds to cysteine 170 of ACSL4, inhibiting its activity to suppress lipid peroxidation and ferroptosis, thereby alleviating ferroptosis-mediated acute liver injury in mouse models.

Online now! #chembiol

09.07.2025 15:30 β€” πŸ‘ 3    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
Preview
Plasmodium falciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity Nardella et al. repurposed a kinase inhibitor for malaria treatment, addressing the challenge posed by Plasmodium falciparum’s resistance to most existing antimalarial drugs. The inhibitor targets protein kinase 6 and hemozoin formation pathway involved in heme detoxication, highlighting the complexity and potential effectiveness of its antiplasmodial action.

Online now! #chembiol

08.07.2025 15:30 β€” πŸ‘ 3    πŸ” 0    πŸ’¬ 0    πŸ“Œ 1
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Site-resolved assessment of targeted protein degradation Moreno Ballesteros et al. introduce a site-resolved strategy combining genetic code expansion and bioorthogonal chemistry to evaluate how ligand binding sites influence targeted protein degradation. This approach offers a powerful framework to accelerate degrader design, enable target validation, and broadly explore the potential of induced proximity.

Online now! #chembiol

07.07.2025 15:30 β€” πŸ‘ 5    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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Electrochemical sensor toolkit for simultaneous glutamate detection at edge of cleft and peri-soma Liu et al. engineered electrochemical glutamate sensors (eGluSn) by integrating biologically engineered GluR with chemically designed ferrocene groups onto a nanoelectrode. These sensors provide quantitative, real-time measurement of Glu simultaneously at edge of cleft and peri-soma, revealing key roles for non-vesicular release pathways (xCT/hemichannels) in pathological models.
20.06.2025 18:00 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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A cationic amphiphilic drug synergizes with strobilurin fungicides to control fungal-borne plant diseases Laflamme et al. identified CMLD009688 as a compound with activity against the plant fungal pathogen Fusarium graminearum. The authors characterize CMLD009688 as a cationic amphiphile that perturbs vacuolar integrity alone and with strobilurin fungicides. CMLD009688 and strobilurins display efficacy in multiple plant infection models.
20.06.2025 17:01 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Mechanism by which the molecular glue-like verteporfin induces IRE1Ξ± dimerization and activation to synergize with AKT inhibition in breast cancer Liu et al. identify verteporfin as a molecular glue that activates IRE1Ξ±, an endoplasmic reticulum stress sensor. They show that verteporfin induces IRE1Ξ± dimerization and activation, downregulating PTEN and upregulating AKT. Combined with an AKT inhibitor, verteporfin significantly suppresses breast cancer cell growth in vitro and in vivo.
20.06.2025 16:01 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation In this study, Baro et al. present a mechanistic approach for the partial inhibition of N-glycosylation, which enables the delivery of bioavailable small molecules exhibiting anti-tumor activity in EGFR mutant non-small cell lung cancer (NSCLC). These inhibitors not only offer strategies for targeting N-glycosylation but also serve as valuable tools for investigating the roles of OST-A and OST-B in maintaining glycoprotein stability in vivo.
20.06.2025 15:00 β€” πŸ‘ 0    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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EGR2 O-GlcNAcylation orchestrates the development of protumoral macrophages to limit CD8+ T cell antitumor responses Zhang et al. report that glucose-driven O-GlcNAc modification of the transcription factor EGR2 reprograms tumor-associated macrophages to suppress CD8+ T cell-mediated antitumor immunity. This study uncovers how metabolic rewiring in the tumor microenvironment shapes immunosuppressive macrophages, offering insights for targeting macrophage plasticity to enhance cancer immunotherapy.
20.06.2025 14:01 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Charting the development and engineering of CRISPR base editors: lessons and inspirations CRISPR base editors (BEs) are genome editing tools that enable precise nucleotide changes without relying on double-stranded breaks. Zou et al. reviewed the history of BE development and discussed technical challenges and insights from the perspective of protein engineering.
20.06.2025 13:00 β€” πŸ‘ 2    πŸ” 2    πŸ’¬ 0    πŸ“Œ 0
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Flush with insight: Decoding GPCR crosstalk in the spinal defecation center 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.
19.06.2025 21:00 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Two sides of a co(i)ndensate In the June 5th issue of Molecular Cell, Das et al. 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.
19.06.2025 20:00 β€” πŸ‘ 2    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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Integrator: A guardian against RNA-induced chaos In the June 12th issue of Cell, Baluapuri et al. report that loss of the Integrator (INT) complex triggers cellular stress by unleashing aberrant transcription, resulting in production of immunogenic double-stranded RNA. Dissecting early and late consequences of INT depletion, the study exemplifies how transcriptional dysregulation can culminate in profound physiological outcomes.
19.06.2025 19:00 β€” πŸ‘ 4    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
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The critical role of PSAC channel in malaria parasite survival is driven home by phenotypic screening under relevant nutrient levels Irene Molina et al. reveal that compound screening under relevant nutrient levels identified 29 new antimalarial chemotypes targeting the PSAC channel. This underscores the channel’s crucial role in parasite survival, demonstrates the in vivo efficacy of PSAC inhibitors and highlights the importance of physiological conditions in the drug discovery process.
19.06.2025 18:00 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Host-like conditions validate nutrient transport as an antimalarial drug target 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. 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.
19.06.2025 17:00 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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The June issue of Cell Chemical Biology is live! Click here to read more: http://dlvr.it/TLRwBT

19.06.2025 16:02 β€” πŸ‘ 2    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
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Ribosomal RNA transcription regulates splicing through ribosomal protein RPL22 Fan et al. uncovered a mechanism linking rRNA synthesis to spliceosomal regulation. Using large-scale cancer cell line screens with specific RNA polymerase I inhibitors, they identified a non-canonical ribotoxic stress pathway mediated by RPL22, RPL22L1, and MDM4, with RPL22 acting as a master splicing regulator coordinated with rRNA synthesis.

Online now! #chembiol

18.06.2025 15:31 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0
Preview
A cationic amphiphilic drug synergizes with strobilurin fungicides to control fungal-borne plant diseases Laflamme et al. identified CMLD009688 as a compound with activity against the plant fungal pathogen Fusarium graminearum. The authors characterize CMLD009688 as a cationic amphiphile that perturbs vacuolar integrity alone and with strobilurin fungicides. CMLD009688 and strobilurins display efficacy in multiple plant infection models.

Online now! #chembiol

11.06.2025 15:30 β€” πŸ‘ 3    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
Preview
EGR2 O-GlcNAcylation orchestrates the development of protumoral macrophages to limit CD8+ T cell antitumor responses Zhang et al. report that glucose-driven O-GlcNAc modification of the transcription factor EGR2 reprograms tumor-associated macrophages to suppress CD8+ T cell-mediated antitumor immunity. This study uncovers how metabolic rewiring in the tumor microenvironment shapes immunosuppressive macrophages, offering insights for targeting macrophage plasticity to enhance cancer immunotherapy.

Online now! #chembiol

10.06.2025 15:30 β€” πŸ‘ 0    πŸ” 1    πŸ’¬ 0    πŸ“Œ 0
Preview
Redundancy of the OST catalytic subunit facilitates therapeutic targeting of N-glycosylation In this study, Baro et al. present a mechanistic approach for the partial inhibition of N-glycosylation, which enables the delivery of bioavailable small molecules exhibiting anti-tumor activity in EGFR mutant non-small cell lung cancer (NSCLC). These inhibitors not only offer strategies for targeting N-glycosylation but also serve as valuable tools for investigating the roles of OST-A and OST-B in maintaining glycoprotein stability in vivo.

Online now! #chembiol

09.06.2025 15:30 β€” πŸ‘ 1    πŸ” 0    πŸ’¬ 0    πŸ“Œ 0

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