Bioorganic & Medicinal Chemistry最新文献

{"title":"Synthesis, biological evaluation and validation of IMB-881 derivatives as anti-Gram-negative bacterial agents","authors":"Chao Liu ,&nbsp;Xiaohong Zhu ,&nbsp;Wenjing Shi ,&nbsp;Qionglu Duan ,&nbsp;Min Yuan ,&nbsp;Yifan Zheng ,&nbsp;Yuanjuan Wei ,&nbsp;Baoqing You ,&nbsp;Jing Zhang ,&nbsp;Shuyi Si ,&nbsp;Yan Li","doi":"10.1016/j.bmc.2025.118066","DOIUrl":"10.1016/j.bmc.2025.118066","url":null,"abstract":"<div><div>Infectious diseases caused by drug-resistant bacteria represent one of the most significant global public challenges of this century. There is an urgent need for the treatment of drug-resistant Gram-negative bacterial infections. A series of 3,4-dihydro-2H-[1,3]oxazino[5,6-<em>h</em>]quinoline derivatives were synthesized and evaluated for their antibacterial activity against Gram-negative bacteria including strains from ATCC and clinical isolates, initially revealing the structure–activity relationship. Among them, 22 compounds demonstrated inhibitory activity (MICs: 3.125–12.5 μg/mL) against <em>Escherichia coli</em> (<em>E. coli</em>) ATCC 25922 and <em>Acinetobacter baumannii</em> (<em>A. baumannii</em>) ATCC 19606. Among these, 7 compounds exhibited good inhibitory activity against MDR <em>A. baumannii</em> clinical isolates, with MICs ranging from 3.125 to 12.5 μg/mL. Most of these compounds also showed lower cytotoxicity than IMB-881. Notably, 2 compounds, <strong>4n1</strong> and <strong>4b3</strong>, significantly extended the survival of <em>Galleria mellonella</em> larvae infected with <em>E. coli</em>. Mechanism studies have revealed that compounds <strong>4n1</strong> and <strong>4b3</strong> might disrupt the interaction between LptA and LptC, showing moderate affinity for LptA protein. These compounds also induce abnormal bacterial morphology and cause outer membrane damage. This finding provides a novel class of antibiotic sensitizers with the potential to effectively fight against <em>E. coli</em> and <em>A. baumannii</em>.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118066"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Japanese pharmaceutical chemistry","authors":"Kazumasa Aoki,&nbsp;Hideko Nagasawa","doi":"10.1016/j.bmc.2025.118068","DOIUrl":"10.1016/j.bmc.2025.118068","url":null,"abstract":"","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118068"},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing into the plasma stability and microsomal stability of thiol-based prodrug derivatives: Using IYS-15, an HDAC inhibitor as the model thiol","authors":"Lingxuan Zhu ,&nbsp;Wei Wang ,&nbsp;Qingjiao Li ,&nbsp;Hanqi Wang ,&nbsp;Xinsheng Lei","doi":"10.1016/j.bmc.2025.118064","DOIUrl":"10.1016/j.bmc.2025.118064","url":null,"abstract":"<div><div>Thiols have interesting bio-chemical properties and can be found in a number of approved drugs. However, some thiols exhibited poor plasma stability and microsomal stability, leading to poor <em>in vivo</em> activity and poor oral bio-availability, in spite of their potent activity <em>in vitro</em>. Prodrug is a classic strategy to improve drug pharmacokinetics. In this study, we designed and synthesized 25 prodrug derivatives of a potent thiol-based HDAC inhibitor, IYS-15, to explore the structure-plasma stability relationships and structure-microsomal stability relationships in these series. We also tried to identify the main metabolic enzymes participated in the metabolism of some representative thiol-based prodrug derivatives. This work thus presents a comparison between different prodrugs based on the same model thiol, giving insights into the stability profile of the synthesized prodrug derivatives in human plasma and human liver microsomes, and more importantly, might also provide structural guidance to medicinal chemists in the design of thiol-based prodrugs and other novel prodrugs with thiol-based linkers.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118064"},"PeriodicalIF":3.3,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring anticancer properties of new triazole-linked benzenesulfonamide derivatives against colorectal carcinoma: Synthesis, cytotoxicity, and in silico insights","authors":"Belma Zengin Kurt ,&nbsp;Özge Özmen ,&nbsp;Dilek Öztürk Civelek ,&nbsp;Halil Şenol ,&nbsp;Fatih Sonmez","doi":"10.1016/j.bmc.2025.118060","DOIUrl":"10.1016/j.bmc.2025.118060","url":null,"abstract":"<div><div>This study reports the design, synthesis, and characterization of a novel series of benzene sulfonamide-triazole hybrid derivatives, to evaluate their anticancer potential against colorectal cancer. The synthesized compounds were characterized using NMR and HRMS spectroscopic techniques. <em>In vitro</em> cytotoxicity assessments revealed that compounds <strong>5g</strong> and <strong>5j</strong> exhibited significant anticancer effects. <strong>5g</strong> showed the highest potency in the DLD-1 cell line (IC₅₀ = 11.84 µM), while <strong>5j</strong> demonstrated robust activity in the HT-29 cell line (IC₅₀ = 9.35 µM). Apoptotic analysis indicated that compound <strong>5g</strong> effectively induced early and total apoptosis, surpassing the chemotherapeutic agent 5-fluorouracil (5-FU), highlighting its therapeutic potential. Molecular docking studies showed strong binding interactions with key proteins involved in colorectal cancer progression, such as TGFβ2 and VEGFR1. <strong>5j</strong> displayed a high binding affinity for TGFβ2 (MM-GBSA ΔG = −92.52 kcal/mol) and <strong>5g</strong> showed promising interactions with VEGFR1 (ΔG = −70.63 kcal/mol). Molecular dynamics simulations confirmed the stability of the ligand–protein complexes, indicating potential as targeted therapeutic agents. Compounds <strong>5g</strong> and <strong>5j</strong> demonstrate significant promise for further development in colorectal cancer treatment.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118060"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of a 6-arylaminobenzamide lead derivative as a potential core scaffold for S1P5 positron emission tomography radiotracer development","authors":"Robert C. Shaw ,&nbsp;Timaeus E.F. Morgan ,&nbsp;Holly McErlain ,&nbsp;Carlos J. Alcaide-Corral ,&nbsp;Adam D. Waldman ,&nbsp;Dmitry Soloviev ,&nbsp;David Y. Lewis ,&nbsp;Andrew Sutherland ,&nbsp;Adriana A.S. Tavares","doi":"10.1016/j.bmc.2024.118057","DOIUrl":"10.1016/j.bmc.2024.118057","url":null,"abstract":"<div><div>Sphingosine-1-phosphate-5 receptors (S1P₅) are predominantly expressed in oligodendrocytes and as a result have been proposed as an important target in Multiple Sclerosis (MS). Selective S1P₅ radiotracers could enable <em>in vivo</em> positron emission tomography (PET) imaging of oligodendrocytes activity. Here we report the synthesis, radiolabelling and first preclinical evaluation of the pharmacokinetics and binding properties of a lead 6-arylaminobenzamide derivative, 6-(mesitylamino)-2-methoxy-3-methylbenzamide (also named as TEFM180), as a potential core scaffold for development of novel S1P₅ PET radiotracers. Following intravenous bolus injection, TEFM180 was found to quickly enter the brain with good brain:blood ratios and subsequent rapid clearance. Autoradiography studies showed that [³H]TEFM180 had a high affinity for its target (K_D = 2.8 nM), with moderate levels of non-displaceable binding. Distribution of [³H]TEFM180 in the brain was found to be consistent with S1P₅ expression and showed a binding potential (BP) of &gt;2–3 in white matter rich regions. Overall, TEFM180 offers a good initial platform for development of future radiotracers targeting S1P₅.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118057"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aspirin-based PROTACs as COX-2 degraders for anti-inflammation","authors":"Xuan-Jie Yu ,&nbsp;Li-Li Chen ,&nbsp;Zhi-Jie Ren ,&nbsp;Yan-Peng Li ,&nbsp;Jia-Yu Chen ,&nbsp;Yu-Xi Zhao ,&nbsp;Jian-Bing Jiang","doi":"10.1016/j.bmc.2025.118061","DOIUrl":"10.1016/j.bmc.2025.118061","url":null,"abstract":"<div><div>Cyclooxygenase-2 (COX-2) is a key enzyme in the biosynthesis of prostaglandins and plays a special role in the process of inflammatory response. COX-2 is a target of non-steroidal anti-inflammatory drugs (NSAIDs), which can effectively relieve inflammation, pain and fever responses by inhibiting COX-2. Despite the significant study progress of inhibitors targeting COX-2, the development of COX-2 degraders remains insufficient. Proteolysis targeting chimaeras (PROTACs) have recently emerged as a fascinating technology for targeted protein degradation and drug discovery. In this report, we present the design, synthesis and detection of aspirin-based PROTACs that demonstrate effective ubiquitin–proteasome pathway degradation of COX-2 in lipopolysaccharide-stimulated RAW264.7 cells, and the aspirin-based negative PROTACs does not promote the degradation of COX-2. Moreover, we show AspPROTACs could significantly affect proteasome degradation and inflammatory signaling pathways through quantitative proteomic data analysis. These COX-2 degraders offer valuable chemical tools and novel insights for research in anti-inflammatory drugs.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118061"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and antitumor effects of novel betulinic acid derivatives bearing electrophilic moieties","authors":"Sen Cai ,&nbsp;Xiuhan Guo ,&nbsp;Haozhe Yang ,&nbsp;Tianyu Zhao ,&nbsp;Yueqing Li ,&nbsp;Ning Deng ,&nbsp;Zhigang Gao ,&nbsp;Qingwei Meng ,&nbsp;Xiaorui Li ,&nbsp;Shisheng Wang","doi":"10.1016/j.bmc.2025.118062","DOIUrl":"10.1016/j.bmc.2025.118062","url":null,"abstract":"<div><div>Betulinic acid (BA) is a kind of naturally occurring lupane pentacyclic triterpenoid, possessing various biological activities including antiviral, anti-inflammatory and antitumor activity. Covalent inhibitors, characterized by electrophilic warheads that form covalent bonds with specific amino acid residues of target proteins, have garnered enormous attention in anticancer agent discovery over the past decade owing to their exceptional selectivity and efficacy. In this study, BA was structurally modified with electrophilic groups, and 23 derivatives of BA were synthesized. Most of these BA derivatives exhibited improved antiproliferative activity against MCF-7, HeLa, MDA-MB-231 cells in MTT assay, especially the compound <strong>15b</strong> (IC₅₀ = 1.09 μM against MCF-7 cells). Further study demonstrated that 1<strong>5b</strong> inhibited the migration and clone formation of MCF-7 cells, induced the apoptosis, autophagy and cycle arrest at G2/M phase in MCF-7 cells, and promoted the production of intracellular reactive oxygen species (ROS). Western blot analysis showed that <strong>15b</strong> inhibited AKT/mTOR signaling pathway in MCF-7 cells. In addition, <strong>15b</strong> reversed the resistance of JIMT-1 cells to trastuzumab, which might be related to the inhibition of AKT/mTOR pathway. Finally, <strong>15b</strong> significantly inhibited the growth of tumor in the breast cancer xenograft mouse model with 36 % inhibition rate of tumor growth and without significant reduction of mouse body weight.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118062"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and evaluation of the pharmacological activity of novel NMDA receptor antagonists based on the germacrone scaffold","authors":"Pengfei Song ,&nbsp;Chao Ma ,&nbsp;Shi Wang ,&nbsp;Yue Zhang ,&nbsp;Lang Xu ,&nbsp;Fang Fang ,&nbsp;Xian Huang ,&nbsp;Yuanhu Zhang ,&nbsp;Qingqiu Mao ,&nbsp;Chaohui Shi ,&nbsp;Maosheng Cheng ,&nbsp;Yang Xu","doi":"10.1016/j.bmc.2025.118063","DOIUrl":"10.1016/j.bmc.2025.118063","url":null,"abstract":"<div><div>The NMDA receptor has long attracted researchers’ attention due to its potential as a drug target and its central role in the central nervous system. The NMDA receptor is a ligand-gated and voltage-dependent ion channel widely distributed in the central nervous system. In this study, we employed a drug design strategy combining “molecular assembly” and “combinatorial chemistry.” By reducing the carbonyl group of germacrone to a hydroxyl group and esterifying it with alanine and linarinic acid, we successfully obtained nine novel germacrone derivatives through two rounds of structural optimization. We evaluated the neuroprotective activity of these nine derivatives using the MTT assay. The results revealed that compound C1 exhibited particularly outstanding activity, achieving a cell protection rate of 29.63 ± 1.56 % at a concentration of 0.05 μM, outperforming the positive control drug, ifenprodil. Further experiments on NMDA-induced Ca²⁺ influx verified that the action site of compound C1 was the NMDA receptor, and demonstrated its superior antagonistic effect on the NMDA receptor compared to germacrone and ifenprodil. Additionally, molecular docking studies and ADMET property predictions were conducted for compound C1. The results showed that compound C1 tightly bound to the active site of the NMDA receptor and possessed favorable pharmacokinetic properties. In conclusion, compound C1, characterized by a germacrone-linarinic acid structure, not only exhibits strong antagonistic effects on the NMDA receptor but also demonstrates excellent pharmacokinetic properties, indicating its potential for further development as a therapeutic drug for central nervous system diseases.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118063"},"PeriodicalIF":3.3,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics","authors":"Peter W. Jurutka ,&nbsp;Zainab Khan ,&nbsp;Ichiro Kaneko ,&nbsp;Michael A. Sausedo ,&nbsp;Pritika H. Shahani ,&nbsp;Mairi MacNeill ,&nbsp;Aleksandra Grozic ,&nbsp;Jaskaran Bhogal ,&nbsp;Johnathon Swierski ,&nbsp;Michael R. Wentzel ,&nbsp;Christine Chhun ,&nbsp;Michael T. Applegate ,&nbsp;San Raban ,&nbsp;Samir Ibrahim ,&nbsp;Karar Alwaeli ,&nbsp;Tracie L. Feldman ,&nbsp;Kayla J. Pomeroy ,&nbsp;Joseph T. Sarnowski ,&nbsp;Natalia Nguyen ,&nbsp;Joseph W. Ziller ,&nbsp;Carl E. Wagner","doi":"10.1016/j.bmc.2024.118059","DOIUrl":"10.1016/j.bmc.2024.118059","url":null,"abstract":"<div><div>Six pyridine analogs of (<em>E</em>)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid—or <strong>CD3254</strong> (<strong>11</strong>)—in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1<em>H</em>-benzo[<em>d</em>][1,2,3]triazole-5-carboxylic acid (<strong>CBt-PMN</strong> or <strong>23</strong>) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (<strong>1</strong>), an FDA-approved drug for cutaneous <em>T</em>-cell lymphoma (CTCL). Treatment with <strong>1</strong> often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay. The EC₅₀ values for these analogs, and their corresponding effectiveness in activating both LXR/LXRE and the Sterol Regulatory Element Binding Protein (SREBP) promoter in comparison to <strong>1</strong>, suggests that these compounds likely display a range of therapeutic potential and differential side effect profiles. Several analogs also exhibited reduced retinoic-acid-receptor (RAR) cross-signaling implying that they possess enhanced selectivity towards activation of cellular RXR versus RAR pathways. These results show that modifying potent rexinoids such as <strong>CD3254</strong> or partial agonists such as <strong>CBt-PMN</strong> can result in improved target receptor selectivity and enhanced potency, such as compounds <strong>26</strong>, <strong>27</strong> and <strong>28</strong> in this study, compared with approved therapeutics such as compound <strong>1</strong>, where these three compounds exhibited similar potency as <strong>1</strong>, but <strong>26</strong> and <strong>27</strong> lower RAR and SREBP activation than <strong>1</strong>.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118059"},"PeriodicalIF":3.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fine-tuning probes for fluorescence polarization binding assays of bivalent ligands against polo-like kinase 1 using full-length protein","authors":"Kohei Tsuji ,&nbsp;Hirokazu Tamamura ,&nbsp;Terrence R. Burke","doi":"10.1016/j.bmc.2024.118055","DOIUrl":"10.1016/j.bmc.2024.118055","url":null,"abstract":"<div><div>Polo-like kinase 1 (Plk1) is an important cell cycle regulator that is a recognized target for development of anti-cancer therapeutics. Plk1 is composed of a catalytic kinase domain (KD), a flexible interdomain linker and a polo-box domain (PBD). Intramolecular protein–protein interactions (PPIs) between the PBD and KD result in “auto-inhibition” that is an essential component of proper Plk1 function. Recently, we developed high-affinity PBD-binding inhibitors using a bivalent approach. These ligands contain the low-nanomolar affinity Plk1 KD-binding inhibitors BI2536 or Wortmannin tethered to the PBD-binding peptide, PLH*SpT (H* represents a –(CH₂)₈Ph group on the histidine side chain π-nitrogen). Due to the extremely high affinity of these bivalent inhibitors, to avoid bottoming out in competitive binding assays, it was necessary to use PLH*SpT in the affinity probe. As reported herein, we have developed fluorescence polarization assays using a new fluorescent probe based on the Plk1 PBD-binding peptide, FDPPLHSpTA. We applied the assay to evaluate the affinities of bivalent inhibitors that possess a variety of PBD-binding peptides having much lower PBD-affinities than PLH*SpT. Tethering BI2536 in these bivalent inhibitors resulted in significant affinity enhancements as compared to the parent monovalent peptides.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"119 ","pages":"Article 118055"},"PeriodicalIF":3.3,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143104563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}