ACS Medicinal Chemistry Letters最新文献

In This Issue, Volume 16, Issue 9 本刊第16卷第9期

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-09-11 DOI: 10.1021/acsmedchemlett.5c00497

Andrew P. Riley,

引用次数: 0

Chelator Optimization and Therapeutic Potential of 188Re-FAPI for FAP-Targeted Radionuclide Therapy 188Re-FAPI螯合剂优化及其在fap靶向放射性核素治疗中的应用潜力

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-09-03 DOI: 10.1021/acsmedchemlett.5c00486

Steven H. Liang*,

{"title":"Chelator Optimization and Therapeutic Potential of 188Re-FAPI for FAP-Targeted Radionuclide Therapy","authors":"Steven H. Liang*, ","doi":"10.1021/acsmedchemlett.5c00486","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00486","url":null,"abstract":"Fibroblast activation protein (FAP) has emerged as a highly promising molecular target for cancer theranostics, with current research prioritizing the optimization of FAP-targeted radiopharmaceutical pharmacokinetics. The development of diverse FAP inhibitor (FAPI) probes conjugated with therapeutic radionuclides has significantly advanced the field of FAP-targeted radionuclide therapy (FAP-TRT). Among available radionuclides, rhenium-188 has emerged as a particularly valuable theranostic radionuclide, offering the rare combination of economical availability, therapeutic β– emissions (Emax = 2.12 MeV), and γ emissions suitable for SPECT imaging (155 keV, 15% abundance). The strategic development of 188Re-labeled FAPI compounds represents a promising approach to enhance the efficacy and clinical translation of FAP-targeted radionuclide therapy. A recent study has developed and evaluated four novel 188Re-labeled FAP inhibitors through rational structure optimization, which provided a cost-effective viable alternative to established therapeutic radionuclides in clinical oncology.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 9","pages":"1697–1702"},"PeriodicalIF":4.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.5c00486","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036680","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}

引用次数: 0

From Bench to Browser: How Reddit Chemists Are Shaping AI, Flow Chemistry, ASOs, and Sustainability in Medicinal Chemistry 从工作台到浏览器：Reddit化学家如何在药物化学中塑造人工智能、流动化学、aso和可持续性

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-09-01 DOI: 10.1021/acsmedchemlett.5c00483

Harsh Mehta*,

引用次数: 0

Characterization of Next-Generation Inhibitors for the Inward-Rectifier Potassium Channel Kir2.1: Discovery of VU6080824 新一代内向整流钾通道Kir2.1抑制剂的表征：VU6080824的发现

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-29 DOI: 10.1021/acsmedchemlett.5c00297

Renn A. Duncan, Daniel H. Haymer, Roman M. Lazarenko, Liangping Li, Yvette Blackwell, Emily L. Days, Srinivasan Krishnan, Analisa Thompson Gray, Olivier Boutaud, Darren W. Engers, Craig W. Lindsley*, Jerod S. Denton* and Aaron M. Bender*,

{"title":"Characterization of Next-Generation Inhibitors for the Inward-Rectifier Potassium Channel Kir2.1: Discovery of VU6080824","authors":"Renn A. Duncan, Daniel H. Haymer, Roman M. Lazarenko, Liangping Li, Yvette Blackwell, Emily L. Days, Srinivasan Krishnan, Analisa Thompson Gray, Olivier Boutaud, Darren W. Engers, Craig W. Lindsley*, Jerod S. Denton* and Aaron M. Bender*, ","doi":"10.1021/acsmedchemlett.5c00297","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00297","url":null,"abstract":"ML133 is a selective inhibitor of the inward-rectifier potassium channel Kir2.1 and has found extensive use as a tool with which to probe Kir biology. Despite its utility as a tool compound, ML133 has only modest on-target potency (manual patch clamp (MPC) Kir2.1 IC50 = 1.5 μM, pH 7.4), and its in vivo pharmacokinetics (PK) were previously uncharacterized. In the present study, we report a next-generation series of Kir2.1 inhibitors based on the ML133 scaffold, along with the rat PK of ML133 and selected analogs. Compound 5s (VU6080824) was ultimately identified as having superior potency to ML133 in both the thallium flux and MPC functional assays and has excellent PK properties suitable for use as an improved Kir2.1 tool compound in rodents.","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 9","pages":"1762–1771"},"PeriodicalIF":4.0,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsmedchemlett.5c00297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145036212","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}

引用次数: 0

Novel Pyrido[4,3-d]pyrimidine Compounds as KRAS Inhibitors 新型吡啶[4,3-d]嘧啶类化合物作为KRAS抑制剂

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-29 DOI: 10.1021/acsmedchemlett.5c00493

Jian Rong, and , Steven H. Liang*,

引用次数: 0

Novel Cyclic Peptides Trapping Interleukin-1β to Relieve Inflammatory and Atherosclerotic Cardiovascular Disease 捕获白细胞介素-1β的新型环状肽可缓解炎症和动脉粥样硬化性心血管疾病

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-29 DOI: 10.1021/acsmedchemlett.5c00495

Qilong Hu, and , Steven H. Liang*,

引用次数: 0

Novel Indazole Propionic Acid Derivatives as AMPK Activators 新型吲哚唑丙酸衍生物作为AMPK活化剂

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-28 DOI: 10.1021/acsmedchemlett.5c00494

Jian Rong, and , Steven H. Liang*,

引用次数: 0

Development of Bicyclic Compounds Containing a Tertiary Amine Moiety as T Cell Activators 含叔胺双环化合物作为T细胞活化剂的研究进展

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-28 DOI: 10.1021/acsmedchemlett.5c00496

Taoqian Zhao, and , Steven H. Liang*,

引用次数: 0

Discovery of Potent and Selective Quinoline-Based Toll-like Receptor 9 Antagonists 强效选择性喹啉类toll样受体9拮抗剂的发现

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-26 DOI: 10.1021/acsmedchemlett.5c00248

Xue Song, Chen-Guo Feng, Chen Wang, Jay Cheng* and Guo-Qiang Lin*,

引用次数: 0

Design, Synthesis, and Biological Evaluation of Sulfonamide Derivatives as Potent CDK9 Inhibitors 磺胺衍生物作为有效CDK9抑制剂的设计、合成和生物学评价

IF 4 3区医学

ACS Medicinal Chemistry Letters Pub Date : 2025-08-26 DOI: 10.1021/acsmedchemlett.5c00430

Yifang Liu, Zexu Wang, Yifan Xu, Liyan Yang, Xiaolei Yang, Zhiyu Li, Jinlei Bian, Jubo Wang*, Lixia Pan* and Tizhi Wu*,

引用次数: 0