Bioorganic & Medicinal Chemistry Letters最新文献

{"title":"Synthesis and anti-breast cancer evaluation of new bakuchiol derivatives.","authors":"Hong-Mei Li, Jing Zhu, Ke Zhong, Jie Chen, Long Zhao, Zhen-Hai Zhang, Cheng-Zhu Wu","doi":"10.1016/j.bmcl.2025.130361","DOIUrl":"10.1016/j.bmcl.2025.130361","url":null,"abstract":"<p><p>In this study, we semi-synthesized nineteen new derivatives of bakuchiol and evaluated their anti-breast cancer properties. Among them, compound 19 stood out as the most effective demonstrating significant cytotoxic activity against MDA-MB-231 cells, with IC₅₀ values of 4.13 μM. Notably, the cytotoxicity of compound 19 towards normal mouse hepatocytes (Aml-12) cells was considerably lower, with IC₅₀ values of 31.60 μM. Our findings indicated that compound 19 triggered apoptosis in MDA-MB-231 cells by increasing the levels of Bax and Cyt C, reducing Bcl-2, and initiating caspase-3 cleavage. It also suppressed the invasion and migration of MDA-MB-231 cells by down-regulating MMP-2 and MMP-9 expression and up-regulating E-cadherin protein levels. We further demonstrated that compound 19 significantly suppressed tumor growth in nude mice xenografted with MDA-MB-231 cells.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130361"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and structural-activity relationship of N-benzyl-2-fluorobenzamides as EGFR/HDAC3 dual-target inhibitors for the treatment of triple-negative breast cancer.","authors":"Gong-Hui Ge, Shuai Guo, Ting-Ting Li, Yan-Ping Wang, Li-Rong Liu, Wen-Hui Yu, Hao Hu, Yi-Meng Zheng, Jing-Han Yan, Ying-Hao Sun, Jing-Wei Liang, Fan-Hao Meng, Ting-Jian Zhang","doi":"10.1016/j.bmcl.2025.130362","DOIUrl":"10.1016/j.bmcl.2025.130362","url":null,"abstract":"<p><p>Epidermal growth factor receptor (EGFR) and histone deacetylase 3 (HDAC3) synergistically drive malignant progression in triple-negative breast cancer (TNBC). In this study, a series of N-benzyl-2-fluorobenzamide derivatives (11-43) were identified as EGFR/HDAC3 dual-target inhibitors. Among them, compound 38 exhibited the most promising activity, with IC₅₀ values of 20.34 nM and 1.09 μM against EGFR and HDAC3, respectively. Molecular modeling revealed that the 2-fluorobenzamide moiety of 38 chelates with Zn²⁺ in the active channel of HDAC3, while the 4-fluorobenzyl group occupies the ATP-binding pocket of EGFR, exercising a dual-target binding function. In vitro experiments demonstrated that 38 exhibited superior anti-proliferative activity (IC₅₀ = 1.98 μM) against MDA-MB-231 cells compared to chidamide (IC₅₀ = 24.37 μM), inducing 74.15 % inhibition of cell migration and 57.4 % late-stage apoptosis. In vivo studies revealed that 38 (30 mg/kg/day) suppressed tumor growth by 34.78 % without significant toxicity. Collectively, 38 represents a novel dual EGFR/HDAC3 inhibitor that shows promising potential for providing new therapeutic insights into TNBC treatment.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130362"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of pisiferic acid analogues and their anti-adipogenic effect in 3T3-L1 adipocytes.","authors":"Ayako Oshika, Sayumi Ono, Haruka Iwano, Manami Toda, Risa Obayashi, Yuna Takagi, Mako Higashitani, Satomi Fukuoka, Miduki Furukawa, Karen Yagami, Rena Okamura, Natsumi Futoi, Hiroki Yoshioka, Reiko Yano, Koji Yoshida, Hyun-Sun Park, Tomoyo Hasuda, Yukio Hitotsuyanagi, Koichi Takeya, Tomohiro Yamaguchi, Yutaka Aoyagi","doi":"10.1016/j.bmcl.2025.130354","DOIUrl":"10.1016/j.bmcl.2025.130354","url":null,"abstract":"<p><p>12-O-alkyl, acyl, and phenylcarbamoyl, and 11-bromo-7-oxo analogues were prepared from pisiferic acid from Chamaecyparis pisifera, and evaluated anti-adipogenic activity. Among them, pisiferic acid and methyl 12-O-phenylcarbamoylpisiferic acid methyl ester showed relatively high anti-adipogenic effect in 3T3-L1 adipocytes and should be thought to be potential candidates for anti-obesity drug.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130354"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient synthesis, stability-guided optimization and anti-ulcerative colitis evaluation of bee venom peptide melittin.","authors":"Cheng-Jian Pang, Jing-Fang Yao, Qiu-Lan Lv, Li-Ze Zhang, Qian-Yao Yu, Li Zeng, Yun-Kun Qi","doi":"10.1016/j.bmcl.2025.130357","DOIUrl":"10.1016/j.bmcl.2025.130357","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is considered as one of the most prevalent inflammatory bowel diseases (IBDs), which increases risks for colectomy and colorectal cancer. However, due to moderate efficiency and potential side effects of first-line drugs, it is desirable to develop more efficient anti-UC agents. The natural peptide Melittin, which is the main active ingredient of bee venom, is considered as a potential scaffold for the development of anti-UC drugs. Nevertheless, as a linear amphipathic peptide, Melittin could be degraded by various proteases, suffering from poor stability and short half-lives. Previous studies on structural optimization or the potential of Melittin-derived peptides for anti-UC applications still remain limited. In this study, the stability-guided optimization and anti-UC evaluation were conducted on Melittin. The robust synthetic strategy, in vivo anti-UC activity, and anti-inflammatory mechanism were investigated. Compared with Melittin, the derived peptides represented by PCJ-675 were found to exhibit improved proteolytic stability. In the dextran sulfate sodium (DSS)-induced UC mice model, PCJ-675 could significantly alleviate both colon shortening and suppress inflammation symptoms in colon tissue. The western blotting and biochemical indicators suggested that the oral administration of PCJ-675 could protect the colon in colitis mice by inhibiting both the excessive activation of the inflammation-related TLR4/NF-κB pathway and the overexpression of pro-inflammatory cytokines (eg, IL-1β, IL-6, and TNF-α). Collectively, this study not only stablished robust strategies to improve the stability and anti-UC potential of Melittin, but also provided valuable references for the future development of natural cytotoxic peptides based anti-UC agents.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130357"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"¹¹C-labeling of 20(S)-protopanaxadiol, an aglycon of ginsenoside, based on the use of Pd(0)-mediated rapid C-[¹¹C]methylation of boronic precursors.","authors":"Yoshiki Ooshima, Hiroko Koyama, Aya Ogata, Hiroshi Ikenuma, Takashi Yamada, Hiroyuki Kojima, Takashi Kato, Yasuyuki Kimura, Masaaki Suzuki","doi":"10.1016/j.bmcl.2025.130356","DOIUrl":"10.1016/j.bmcl.2025.130356","url":null,"abstract":"<p><p>Ginsenosides, the pharmacologically active components of Panax ginseng, are widely used in herbal medicine and reportedly exert diverse biological effects, including anticancer, anti-inflammatory, and neuroprotective activities. However, their pharmacological mechanisms remain poorly understood, owing to the lack of chemical probes suitable for in vivo analyses. Herein, we report the development of a ¹¹C radiolabeling of 20(S)-protopanaxadiol (PPD), a major aglycone-type active ginsenoside metabolite, for positron emission tomography (PET) imaging. For the ¹¹C labeling of PPD, we focused on the terminal vinyl methyl group of the dammarane-type triterpene backbone, a common structural element found in ginsenosides. A boronic precursor applicable for rapid ¹¹C-methylation was efficiently synthesized via steps focusing on the controlled cross-metathesis of an internal olefin. The subsequent Pd(0)-mediated rapid ¹¹C-methylation was conducted in N,N-dimethylformamide (DMF)/H₂O using [Pd₂(dba)₃], P(o-tolyl)₃, and sodium ascorbate, which functioned as a base and a radical scavenger. After formulation, the resulting [¹¹C]PPD was obtained in a decay-corrected radiochemical yield of 15 ± 2 % (n = 3), with a total radioactivity of 1.0 ± 0.3 GBq (n = 3) and molar activity of 124 ± 7 GBq/μmol (n = 3). Radiochemical purity was ≥99 %, and the total synthesis time was 29 min. Using [¹¹C]PPD, PET imaging of the brains of healthy rats and abdomens of healthy mice demonstrated low brain uptake and pronouncedly clear hepatobiliary excretion of radiolabeled species. These findings may provide a foundation for the general labeling of ginsenoside structures with ¹¹C radioisotopes, thereby enabling systematic in vivo pharmacokinetic analyses of PPD derivatives to advance ginsenoside-based drug development.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130356"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluorogenic rhodamine B derivatives that become brighter at neutral pH.","authors":"Hidetoshi Kajino, Justin H Kwon, Evan W Miller","doi":"10.1016/j.bmcl.2025.130422","DOIUrl":"https://doi.org/10.1016/j.bmcl.2025.130422","url":null,"abstract":"<p><p>Rhodamines are useful fluorescent molecules for activity-based sensing. One powerful design strategy is to exploit changes in the open/closed equilibrium of rhodamine amides. In the context of amide derivatives of rhodamine B, a prototypical member of the rhodamine family, this strategy has been especially useful in the development of activity-based indicators for protons and metal ions. This is because at neutral pH, the closed form of rhodamine B amides dominates, making this otherwise bright and fluorescent dye non-fluorescent. At acidic pH, the equilibrium favors the open form. Despite a wealth of methods to trigger Lewis acid-mediated fluorogenicity of rhodamine B amides, there are far fewer ways to shift the open-close equilibrium to favor the open form at neutral pH. Here, we demonstrate that a simple substitution substantially shifts the native rhodamine B amide equilibrium to favor the open, fluorescent form at neutral pH. Rhodamine B derivatives with an N-(2'-carboxy)-phenyl substitution (an ortho anthranilic acid, RhoB-AA) show strong absorbance and emission at pH 7.2, up to ~1500× greater than their unsubstituted N-phenyl derivatives (RhoB-Ph). The fluorescence of RhoB-AA at neutral pH is dependent on the free carboxylic acid. Esters of RhoB-AA are also ~1500× less fluorescent than RhoB-AA and have optical properties nearly identical to the unsubstituted RhoB-Ph. Esters of RhoB-AA can be converted by esterases to the fully fluorescent RhoB-AA, demonstrating that the simple ortho anthranilic acid substitution is a powerful strategy for activity-based sensing with rhodamine amides at neutral pH.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130422"},"PeriodicalIF":2.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR-targeted extracellular vesicles loaded with doxorubicin for enhanced chemotherapy in non-small cell lung cancer via bioorthogonal click chemistry.","authors":"Xiaoli Li, Xianbing Zeng, Xiaomao Hu","doi":"10.1016/j.bmcl.2025.130419","DOIUrl":"https://doi.org/10.1016/j.bmcl.2025.130419","url":null,"abstract":"<p><p>In the field of non-small cell lung cancer (NSCLC) treatment, targeted drug delivery to epidermal growth factor receptor (EGFR)-overexpressing tumors remains a significant challenge. This study aims to tackle this issue by engineering extracellular vesicles (EVs) derived from 293 T cells. Through azide-alkyne cycloaddition, EVs were functionalized with GE11 peptides (GE11-EVs), and loaded with doxorubicin to form GE11&DOX@EVs. We conduted Ac4ManNAz metabolic labeling to facilitate the site-specific conjugation of GE11 peptides and fluorescent probes onto the membranes of EVs. Then we comprehensively assessed the targeting efficiency, drug-loading capacity, and therapeutic efficacy of GE11-EVs in A549 NSCLC cells and xenograft models. In vitro experiments demonstrated significantly enhanced uptake of GE11-EVs by EGFR-positive A549 cells compared to unmodified EVs, along with markedly improved cytotoxicity of GE11&DOX@EVs against tumor cells (IC₅₀: 1.6 μg/mL vs. 3.96 μg/mL for free doxorubicin, P < 0.01) and induction of mitochondrial membrane depolarization. Mechanistically, GE11&DOX@EVs upregulated pro-apoptotic proteins (caspase-3/8/9 and Bax) and downregulated anti-apoptotic BCL-2, significantly enhancing apoptosis compared to free DOX. In vivo imaging revealed a two-fold greater tumor accumulation of GE11-EVs than unmodified EVs at 24 h post-injection. GE11&DOX@EVs treatment suppressed tumor growth by 73.7 % in A549 xenografts, significantly outperforming both free doxorubicin (24.9 %) and DOX@EVs (58.6 %) groups (P < 0.05), with minimal systemic toxicity. Future research could further explore the clinical translation potential of this bioorthogonal platform for precision engineering of EVs in NSCLC therapy.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130419"},"PeriodicalIF":2.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, structure-activity relationships of carnosol derivatives for cancer-associated cachexia.","authors":"Juan Wang, Qiang Wang, Kun Wei, Xiaojuan Pan, Xuan Liu, Xiongwen Zhang, Xianrong Cai, Meng Fan, Chunru Cheng","doi":"10.1016/j.bmcl.2025.130420","DOIUrl":"https://doi.org/10.1016/j.bmcl.2025.130420","url":null,"abstract":"<p><p>Cancer-associated cachexia, marked by progressive muscle atrophy and metabolic dysfunction, poses a significant therapeutic challenge. To address carnosol's metabolic instability, we rationally designed 35 derivatives by replacing its oxidation-prone 11,12-phenolic groups with oxazole rings or aryl moieties. SAR-guided optimization identified 10 as the lead compound. In C26 tumor-conditioned models, 10 attenuated myotube atrophy (67.08 % reversal) and adipocyte lipolysis. In C26 tumor-bearing mice, 10 alleviated cachexia-related weight loss without altering tumor progression. Pharmacokinetic studies revealed enhanced stability: a half-life of 11.1 h and an AUC_0-t of 8369 ng/mL. These results position 10 as a promising therapeutic candidate for cancer cachexia, while offering a strategic framework for rational optimization of natural product.</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130420"},"PeriodicalIF":2.2,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,4-Naphthoquinone thiazole urea hybrids bearing morpholine/piperazine: synthesis, crystal structure, aldose reductase and α-glycosidase enzyme inhibition, molecular docking, and electrochemical interaction with dsDNA.","authors":"Cagla Efeoglu, Selenay Sadak, Ertan Sahin, Yeliz Demir, Cüneyt Türkeş, Bengi Uslu, Yahya Nural","doi":"10.1016/j.bmcl.2025.130417","DOIUrl":"10.1016/j.bmcl.2025.130417","url":null,"abstract":"<p><p>In this study, new 1,4-naphthoquinone thiazole urea hybrids bearing morpholine (3a-d) or piperazine (3e-h) moiety were synthesized in 76-89 % yields and characterized by ¹H NMR, ¹³C NMR, FT-IR, HRMS, and elemental analysis. The stereochemistry of 3d was determined by single crystal x-ray diffraction study. We evaluated the inhibitory potential of these compounds 3a-h on aldose reductase (ALR2) and α-glycosidase enzyme (α-GLY) activity. Our results indicate that these compounds substantially inhibit ALR2 at micromolar doses, with inhibition constants (K_Is) between 0.79 and 2.20 μM and inhibit α-GLY K_I between 0.67 and 2.82 μM. Molecular docking simulations were utilized to elucidate inhibitory effects and establish structure-activity relationships for the synthesized compounds. DNA interaction studies are of great importance for the synthesis of new drugs and for studying the behavior and mechanisms of action of synthesized drug molecules. Herein, the interaction of 3d selected as a model compound with ct-dsDNA was investigated in the solution phase by the electrochemical method of differential pulse voltammetry (DPV). The decrease in the peak current value of 3d after the addition of the DNA solution confirmed the interaction. Limits of detection (LOD) and quantification (LOQ) for the interaction were found to be 0.099 ppm and 0.327 ppm in the concentration range of 0.348 ppm to 0.739 ppm, respectively. To determine the binding constant, cyclic voltammetry (CV) was utilized and found to be 8.6 × 10² M^-1. Additionally, the type of interaction between the 3D molecule and DNA was investigated and supported by molecular docking and Fourier transformed infrared spectroscopy (FTIR).</p>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":" ","pages":"130417"},"PeriodicalIF":2.2,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and evaluation of [18F]AlF-NOTA-RIDGE11: A novel retro-inverso peptide PET probe for EGFR imaging","authors":"Lu Bai ,&nbsp;Haoran Liang ,&nbsp;Dazhi Shi ,&nbsp;Yijin Zou ,&nbsp;Wenhao Jiang ,&nbsp;Xiaxia Li ,&nbsp;Xiue Feng ,&nbsp;Xiaohong Huang ,&nbsp;Shun Huang","doi":"10.1016/j.bmcl.2025.130418","DOIUrl":"10.1016/j.bmcl.2025.130418","url":null,"abstract":"<div><div>The overexpression of epidermal growth factor receptor (EGFR) in multiple cancers establishes it as a valuable biomarker for targeted therapies and non-invasive imaging. This study developed a novel peptide-based PET probe targeting EGFR, [¹⁸F]AlF-NOTA-RI^DGE11, by conjugating a NOTA chelator to the D-type retro-inverso isomer of ^LGE11 (RI^DGE11) to enhance metabolic stability. Molecular docking reveals comparable EGFR binding affinity (−7.1 kcal/mol) to that of the native ^LGE11 peptide (−6.9 kcal/mol). Efficient radiolabeling was achieved within 30 min using the one-step ¹⁸F‑aluminum fluoride method (radiochemical yield of 18.3–28.4 %; radiochemical purity &gt;99 %). The probe demonstrated high hydrophilicity (logD = −3.90 ± 0.01) with excellent stability in both <em>vitro</em> and <em>vivo</em> conditions (&gt; 95 % intact after 2 h in plasma). In EGFR-positive HCT116 cells, [¹⁸F]AlF-NOTA-RI^DGE11 exhibited specific and blockable uptake (60 min: 1.96 ± 0.11 % ID/1 million cells). Micro-PET imaging in HCT116 tumor xenografts revealed moderate tumor uptake (60 min: 1.49 ± 0.37 % ID/g) with rapid clearance from non-target organs, resulting in favorable tumor-to-background ratios (tumor/muscle: 9.24 ± 3.51; tumor/liver: 2.25 ± 0.11). Specificity was confirmed by a significant reduction in tumor uptake (1.32 ± 0.15 % ID/g <em>vs.</em> 0.30 ± 0.04 % ID/g at 60 min; <em>p</em> &lt; 0.01) following co-injection with excess ^LGE11 peptide. Biodistribution analyses corroborated the imaging findings and indicated predominant renal excretion. Kinetic modeling identified a reversible two-tissue compartment model as optimal. While the high hydrophilicity contributes to rapid washout from tumors, [¹⁸F]AlF-NOTA-RI^DGE11 exhibits promising characteristics for <em>in vivo</em> stability and pharmacokinetic properties, demonstrating its potential as a targeted tracer for EGFR-positive tumor imaging. Future studies will focus on probe optimization to enhance tumor retention.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"130 ","pages":"Article 130418"},"PeriodicalIF":2.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}