ACS Chemical Biology最新文献

{"title":"Synthesis of Differentially Halogenated Lissoclimide Analogues To Probe Ribosome E-Site Binding.","authors":"Salvatore Terrosu, Liliia Nurullina, Nantamon Supantanapong, Bonnie S Pak, Sierra Nguyen, Mikael Holm, Cheng Wu, Min Lin, David Horne, Matthew S Sachs, Scott C Blanchard, Marat Yusupov, Christopher D Vanderwal","doi":"10.1021/acschembio.4c00825","DOIUrl":"10.1021/acschembio.4c00825","url":null,"abstract":"<p><p>Halogenated natural products from marine sources often demonstrate potent activity against microorganisms and cancer cell lines. During the last three decades, the lissoclimide class of chlorinated labdane diterpenoids has been characterized with respect to structure and cytotoxic activity. Recently, our laboratories have developed different strategies to produce a broad range of naturally occurring lissoclimides and designed synthetic analogues. This work led to the discovery of a novel halogen-π dispersion interaction between the C2 chloride of chlorolissoclimide and guanine residues in the tRNA exit (E) site of the ribosome. In this study, we aimed to synthesize lissoclimide analogues bearing different substituents in place of the chloride to investigate the importance of the halogen identity for binding, translation inhibition, and cytotoxicity. With previous access to the protio and chloro compounds (haterumaimide Q and chlorolissoclimide), we synthesized two more halogenated variants, fluorolissoclimide and bromolissoclimide, as well as a methylated analogue, methyllissoclimide, to complete a panel of chemical probes for functional and structural studies. Using an integrative approach, we explored the effects of these analogues on the eukaryotic translational machinery in vivo and in vitro. X-ray cocrystal structures with the eukaryotic ribosome were solved for each probe molecule, and the effects on ribosomal thermal stability and FRET-derived ribosome binding constants were determined. Together, these data provide a detailed understanding of the different modes of binding of lissoclimides and insight into their relative activities, which vary according to the substitutions that interact with the eukaryote-specific ribosomal protein eL42. Ultimately, we learned that the presence of a lissoclimide C2-halogen atom─offering a potentially stabilizing halogen-π interaction─appears to facilitate or to synergize with a hydrogen-bonding interaction between the C7-hydroxyl group and the backbone of the ribosomal protein eL42, leading to stronger translation inhibition. We therefore conclude that the C2-halogen and C7-hydroxyl groups are critical contributors to potency, and this idea is borne out in the observations of reduced biological activities in the absence of either group.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":"858-869"},"PeriodicalIF":3.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure","authors":"Jie Sun,&nbsp;Kyunga Lee,&nbsp;Sergei Kutseikin,&nbsp;Adrian Guerrero,&nbsp;Bibiana Rius,&nbsp;Aparajita Madhavan,&nbsp;Chavin Buasakdi,&nbsp;Ka-Neng Cheong,&nbsp;Priyadarshini Chatterjee,&nbsp;Dorian A. Rosen,&nbsp;Leonard Yoon,&nbsp;Maziar S. Ardejani,&nbsp;Alejandra Mendoza,&nbsp;Jessica D. Rosarda,&nbsp;Enrique Saez*,&nbsp;Jeffery W. Kelly* and R. Luke Wiseman*,&nbsp;","doi":"10.1021/acschembio.4c0086710.1021/acschembio.4c00867","DOIUrl":"https://doi.org/10.1021/acschembio.4c00867https://doi.org/10.1021/acschembio.4c00867","url":null,"abstract":"<p >Activation of the IRE1/XBP1s signaling arm of the unfolded protein response (UPR) has emerged as a promising strategy to mitigate etiologically diverse diseases. Despite this promise, few compounds are available to selectively activate IRE1/XBP1s signaling to probe the biologic and therapeutic implications of this pathway in human disease. Recently, we identified the compound IXA4 as a highly selective activator of protective IRE1/XBP1s signaling. While IXA4 has proven useful for increasing IRE1/XBP1s signaling in cultured cells and mouse liver, the utility of this compound is restricted by its limited activity in other tissues. To broaden our ability to pharmacologically interrogate the impact of IRE1/XBP1s signaling <i>in vivo</i>, we sought to identify IRE1/XBP1s activators with greater tissue activity than IXA4. We reanalyzed ‘hits’ from the high throughput screen used to identify IXA4, selecting compounds from structural classes not previously pursued. We then performed global RNAseq to confirm that these compounds showed transcriptome-wide selectivity for IRE1/XBP1s activation. Functional profiling revealed compound IXA62 as a selective IRE1/XBP1s activator that reduced Aβ secretion from CHO^7PA2 cells and enhanced glucose-stimulated insulin secretion from rat insulinoma cells, mimicking the effects of IXA4 in these assays. IXA62 robustly and selectively activated IRE1/XBP1s signaling in the liver of mice dosed compound intraperitoneally or orally. In treated mice, IXA62 showed broader tissue activity, relative to IXA4, inducing expression of IRE1/XBP1s target genes in additional tissues such as kidney and lung. Collectively, our results designate IXA62 as a selective IRE1/XBP1s signaling activating compound with enhanced tissue activity, which increases our ability to pharmacologically probe the biologic significance and potential therapeutic utility of enhancing adaptive IRE1/XBP1s signaling <i>in vivo</i>.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 5","pages":"993–1003 993–1003"},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual SLIPT–A Lipid Mimic to Enable Spatiotemporally Defined, Sequential Protein Dimerization","authors":"Kristina V. Bayer,&nbsp;Maedeh Taeb,&nbsp;Birgit Koch,&nbsp;Shige H. Yoshimura and Richard Wombacher*,&nbsp;","doi":"10.1021/acschembio.4c0085610.1021/acschembio.4c00856","DOIUrl":"https://doi.org/10.1021/acschembio.4c00856https://doi.org/10.1021/acschembio.4c00856","url":null,"abstract":"<p >Spatiotemporal control of proteins is crucial for cellular phenomena such as signal integration, propagation, as well as managing crosstalk. In membrane-associated signaling, this regulation is often enabled by lipids, wherein highly dynamic, sequential recruitment of interacting proteins is key to successful signaling. Here, we present dual SLIPT (self-localizing ligand-induced protein translocation), a lipid-analog tool, capable of emulating this lipid-mediated sequential recruitment of any two proteins of interest. Dual SLIPT self-localizes to the inner leaflet of the plasma membrane (PM). There, dual SLIPT presents trimethoprim (TMP) and HaloTag ligand (HTL) to cytosolic proteins of interest (POIs), whereupon POIs fused to the protein tags ^iK6eDHFR, or to HOB are recruited. A systematic extension of the linkers connecting the two mutually orthogonal headgroups was implemented to overcome the steric clash between the recruited POIs. Using Förster resonance energy transfer (FRET), we verify that the resulting probe is capable of simultaneous binding of both proteins of interest, as well as their dimerization. Dual SLIPT was found to be particularly suitable for use in physiologically relevant concentrations, such as recruitment via tightly regulated, transient lipid species. We further expanded dual SLIPT to the photocontrollable dual SLIPT^NVOC, by introducing a photocaging group onto the TMP moiety. Dual SLIPT^NVOC enables sequential and spatiotemporally defined dimerization upon blue light irradiation. Thus, dual SLIPT^NVOC serves as a close mimic of physiology, enabling interrogation of dynamic cytosol-to-plasma membrane recruitment events and their impact on signaling.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 5","pages":"1038–1047 1038–1047"},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.4c00856","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of the RIPK1-Selective Benzo[1,4]oxazepin-4-one Scaffold for the Development of a Type III LIMK1/2 Inhibitor","authors":"Sebastian Mandel,&nbsp;Thomas Hanke,&nbsp;Sebastian Mathea,&nbsp;Deep Chatterjee,&nbsp;Hayuningbudi Saraswati,&nbsp;Benedict-Tilman Berger,&nbsp;Martin Peter Schwalm,&nbsp;Satoshi Yamamoto,&nbsp;Michiko Tawada,&nbsp;Terufumi Takagi,&nbsp;Mahmood Ahmed,&nbsp;Sandra Röhm,&nbsp;Ana Corrionero,&nbsp;Patricia Alfonso,&nbsp;Maria Baena,&nbsp;Lewis Elson,&nbsp;Amelie Menge,&nbsp;Andreas Krämer,&nbsp;Raquel Pereira,&nbsp;Susanne Müller,&nbsp;Daniela S. Krause and Stefan Knapp*,&nbsp;","doi":"10.1021/acschembio.5c0009710.1021/acschembio.5c00097","DOIUrl":"https://doi.org/10.1021/acschembio.5c00097https://doi.org/10.1021/acschembio.5c00097","url":null,"abstract":"<p >Benzoxazepinones have been extensively studied as exclusively selective RIP kinase 1 inhibitors. This scaffold binds to an allosteric pocket created by an αC-out/DFG-out conformation. This inactive conformation results in a large expansion of the kinase back pocket, a conformation that has also been reported for LIM kinases. Scaffold hopping is common in the design of orthosteric kinase inhibitors but has not been explored in the design of allosteric inhibitors, mainly due to the typically exclusive selectivity of type III inhibitors. Here, we hypothesized that the shared structural properties of LIMKs and RIPKs could lead to novel type III LIMK inhibitors using the benzoxazepinone scaffold. We report the discovery of a novel LIMK1/2 inhibitor that relies on this scaffold-based approach. The discovered compound <b>10</b> showed low nanomolar potency on LIMK1/2 and exceptional selectivity, as confirmed by a comprehensive selectivity panel with residual RIPK activity as the only off-target. The study provides one of the few examples for scaffold hopping for allosteric inhibitors, which are usually associated with exclusive target selectivity.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 5","pages":"1087–1098 1087–1098"},"PeriodicalIF":3.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschembio.5c00097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Rapaglutin E as an Isoform-Specific Inhibitor of Glucose Transporter 1","authors":"Marnie Kotlyar,&nbsp;Zufeng Guo,&nbsp;A. V. Subba Rao,&nbsp;Hanjing Peng,&nbsp;Jingxin Wang,&nbsp;Zhongnan Ma,&nbsp;Cordelia Schiene-Fischer,&nbsp;Gunter Fischer and Jun O. Liu*,&nbsp;","doi":"10.1021/acschembio.5c0015210.1021/acschembio.5c00152","DOIUrl":"https://doi.org/10.1021/acschembio.5c00152https://doi.org/10.1021/acschembio.5c00152","url":null,"abstract":"<p >Natural products rapamycin and FK506 are macrocyclic compounds with therapeutic benefits whose unique scaffold inspired the generation and exploration of hybrid macrocycle rapafucins. From this library, a potent inhibitor of the facilitative glucose transporter (GLUT), rapaglutin A (RgA), was previously identified. RgA is a pan-GLUT inhibitor of Class I isoforms GLUT1, GLUT3, and GLUT4. Herein, we report the discovery of rapaglutin E (RgE). Unlike RgA, RgE is highly specific for GLUT1. Further characterization revealed that RgE and RgA likely bound to distinct sites on GLUT1 despite their shared FKBP-binding domain, suggesting that the distinct effector domains of RgE and RgA play key roles in the recognition of GLUTs.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 5","pages":"1004–1009 1004–1009"},"PeriodicalIF":3.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM21-NUP98 Interface Accommodates Structurally Diverse Molecular Glue Degraders","authors":"Yalong Cheng,&nbsp;Longzhi Cao,&nbsp;Panrui Lu,&nbsp;Lei Xue,&nbsp;Xiaomei Li,&nbsp;Qingyang Wang,&nbsp;Dengfeng Dou,&nbsp;Jin Li and Ting Han*,&nbsp;","doi":"10.1021/acschembio.5c0003610.1021/acschembio.5c00036","DOIUrl":"https://doi.org/10.1021/acschembio.5c00036https://doi.org/10.1021/acschembio.5c00036","url":null,"abstract":"<p >Molecular glue degraders enable targeted protein degradation by bridging interactions between target proteins and E3 ubiquitin ligases. Whereas some target-E3 interfaces exhibit the capacity to accommodate structurally diverse degraders, the extent of this adaptability across molecular glue targets remains unclear. We recently identified (<i>S</i>)-ACE-OH as a molecular glue degrader that recruits the E3 ubiquitin ligase TRIM21 to the nuclear pore complex by recognizing NUP98, thereby inducing the degradation of nuclear pore proteins. Here, we analyzed public compound toxicity data across a large collection of cell lines and identified two additional molecular glue degraders, PRLX 93936 and BMS-214662, which engage the TRIM21-NUP98 interface to induce selective degradation of nuclear pore proteins. Additionally, we confirmed that HGC652, another TRIM21-dependent molecular glue degrader, also binds at this interface. Together with our previously characterized degrader (<i>S</i>)-ACE-OH, these findings demonstrate that the TRIM21-NUP98 interface can accommodate structurally diverse molecular glue degraders.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"953–959 953–959"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bringing Histidine Phosphorylation into Light: Role of Chemical Tools","authors":"Solbee Choi,&nbsp;Shin Hyeon Lee and Jung-Min Kee*,&nbsp;","doi":"10.1021/acschembio.5c0010310.1021/acschembio.5c00103","DOIUrl":"https://doi.org/10.1021/acschembio.5c00103https://doi.org/10.1021/acschembio.5c00103","url":null,"abstract":"<p >Histidine phosphorylation is a historically underexplored post-translational modification (PTM). Once deemed “elusive” due to its chemical lability, phosphohistidine (pHis) has recently come to light thanks to emerging chemical tools─including stable pHis analogs, pHis-specific antibodies, and tailored proteomics workflows─that enable its detection and functional analysis. Together, these innovations have led to a surge in the identification of pHis sites and raised awareness of their roles in both bacterial and mammalian systems. New assay systems have also facilitated the characterization of histidine kinases and phosphatases. This Review summarizes recent breakthroughs in pHis research tools, examines the limitations of current approaches, and outlines future tools needed to fully unravel the potential of histidine phosphorylation.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"778–790 778–790"},"PeriodicalIF":3.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmented Acyl-CoA Biosynthesis Promotes Resistance to TEAD Palmitoylation Site Inhibition","authors":"Kayla Nutsch,&nbsp;Marissa N. Trujillo,&nbsp;Lirui Song,&nbsp;Michael A. Erb,&nbsp;Jian Jeffery Chen,&nbsp;James J. Galligan* and Michael J. Bollong*,&nbsp;","doi":"10.1021/acschembio.5c0016210.1021/acschembio.5c00162","DOIUrl":"https://doi.org/10.1021/acschembio.5c00162https://doi.org/10.1021/acschembio.5c00162","url":null,"abstract":"<p >Activation of the YAP-TEAD transcriptional complex drives the growth of several cancer types and is a key resistance mechanism to targeted therapies. Accordingly, a host of pharmacological inhibitors to TEAD family paralogs have been developed, yet little is known as to the resistance mechanisms that might arise against this emerging therapeutic class. Here, we report that genetic augmentation of <i>de novo</i> coenzyme A biosynthesis desensitizes YAP-dependent cancer cells to treatment with TEAD inhibitors, an effect driven by increased levels of palmitoyl-CoA that outcompete drug for engagement of the lipid-binding pocket. This work uncovers a potential therapeutic resistance mechanism to TEAD palmitoylation site inhibition with implications for future combinatorial treatments in the clinic.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"967–975 967–975"},"PeriodicalIF":3.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering the Specificity of Acetyl-CoA Synthetase for Diverse Acyl-CoA Thioester Generation","authors":"Jared R. Cossin,&nbsp;Thaddeus Q. Paulsel,&nbsp;Kim Castelli,&nbsp;Breck Wcisel,&nbsp;Alexandra A. Malico and Gavin J. Williams*,&nbsp;","doi":"10.1021/acschembio.5c0001410.1021/acschembio.5c00014","DOIUrl":"https://doi.org/10.1021/acschembio.5c00014https://doi.org/10.1021/acschembio.5c00014","url":null,"abstract":"<p >CoA thioesters are valuable intermediates in numerous biosynthetic routes and metabolic processes. However, diversifying these compounds and their corresponding downstream products hinges on broadening the promiscuity of CoA ligases that produce them or using additional enzymes to functionalize them. Here, the inherent promiscuity of an acyl-CoA ligase from <i>Pseudomonas chlororaphis</i> was probed with carboxylic acids of varying sizes and functionality. The enzyme was engineered to improve its activity with a diverse panel of acyl-CoA thioesters, including halogenated and oxidized acids, that can be used in downstream biosynthetic production strategies. To demonstrate the utility of the engineered enzyme, a subset of the substrates was leveraged for the complete <i>in situ</i> biosynthesis of a small panel of pyrones via a portion of the archetypal polyketide synthase (PKS), 6-deoxyerythronolide B synthase (DEBS). This approach supports probing the promiscuity of polyketide biosynthesis and the diversification of natural product scaffolds.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"930–941 930–941"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Bioluminescence Imaging of Serum Albumins in Living Mice","authors":"Sung-Bae Kim*,&nbsp;Genta Kamiya,&nbsp;Tadaomi Furuta,&nbsp;Nobuo Kitada,&nbsp;Suresh Thangudu,&nbsp;Arutselvan Natarajan,&nbsp;Shojiro A. Maki and Ramasamy Paulmurugan,&nbsp;","doi":"10.1021/acschembio.4c0074010.1021/acschembio.4c00740","DOIUrl":"https://doi.org/10.1021/acschembio.4c00740https://doi.org/10.1021/acschembio.4c00740","url":null,"abstract":"<p >Bioluminescence (BL) is an emerging optical readout that has been extensively used in various bioassays and molecular imaging systems. In this study, we present the bioanalytical application of marine luciferins as an excellent optical indicator for noninvasive imaging of serum albumins. We synthesized 30 kinds of regioisomeric coelenterazine (CTZ) analogs and investigated their specificities for major serum proteins from various species. The results found that some of the CTZ analogs exhibited surprisingly specific optical signals upon binding with the serum albumins. These CTZ analogs showed diverse emission spectra ranging from 495 to 558 nm according to the albumin species used acting as pseudoluciferases. The selective albumin indicators, <b>TS1</b> and <b>TS2</b>, exhibited long and linear dose–response curves and were sensitive enough to determine clinically normal and abnormal (microalbuminuria) ranges of albumins in saliva and urine. The sensitivity of this assay is superior to that of the conventional Bromocresol purple (BCP) method. We further demonstrated the advantages of the albumin indicators through noninvasive imaging of liver-albumin <i>in vivo</i> in living mice. The <i>in vivo</i> and <i>ex vivo</i> imaging results confirmed that the CTZ analog <b>TS2</b> can sensitively image the liver-albumin <i>in vivo</i> with high signal-to-background ratio. This study paves a new way to make use of CTZ analogs for noninvasive albumin imaging and conceptualizes the pseudoluciferase-based imaging. The distinct <i>in vivo</i> imaging of serum albumins can potentially aid clinicians in providing insight into patients’ liver function and other vital factors needed for whole-body homeostasis.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":"20 4","pages":"802–814 802–814"},"PeriodicalIF":3.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}