Journal of Medicinal Chemistry最新文献

Discovery of BAY-405: An Azaindole-Based MAP4K1 Inhibitor for the Enhancement of T-Cell Immunity against Cancer 发现 BAY-405：一种基于氮杂吲哚的 MAP4K1 抑制剂，可增强 T 细胞的抗癌免疫力

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-27 DOI: 10.1021/acs.jmedchem.4c01325

Jeffrey Mowat, Rafael Carretero, Gabriele Leder, Nuria Aiguabella Font, Roland Neuhaus, Sandra Berndt, Judith Günther, Anders Friberg, Martina Schäfer, Hans Briem, Marian Raschke, Hideki Miyatake Ondozabal, Bernd Buchmann, Ulf Boemer, Bertolt Kreft, Ingo V. Hartung, Rienk Offringa

{"title":"Discovery of BAY-405: An Azaindole-Based MAP4K1 Inhibitor for the Enhancement of T-Cell Immunity against Cancer","authors":"Jeffrey Mowat, Rafael Carretero, Gabriele Leder, Nuria Aiguabella Font, Roland Neuhaus, Sandra Berndt, Judith Günther, Anders Friberg, Martina Schäfer, Hans Briem, Marian Raschke, Hideki Miyatake Ondozabal, Bernd Buchmann, Ulf Boemer, Bertolt Kreft, Ingo V. Hartung, Rienk Offringa","doi":"10.1021/acs.jmedchem.4c01325","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01325","url":null,"abstract":"Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1) is a serine/threonine kinase that acts as an immune checkpoint downstream of T-cell receptor stimulation. MAP4K1 activity is enhanced by prostaglandin E2 (PGE2) and transforming growth factor beta (TGFβ), immune modulators commonly present in the tumor microenvironment. Therefore, its pharmacological inhibition is an attractive immuno-oncology concept for inducing therapeutic T-cell responses in cancer patients. Here, we describe the systematic optimization of azaindole-based lead compound 1, resulting in the discovery of potent and selective MAP4K1 inhibitor 38 (BAY-405) that displays nanomolar potency in biochemical and cellular assays as well as in vivo exposure after oral dosing. BAY-405 enhances T-cell immunity and overcomes the suppressive effect of PGE2 and TGFβ. Treatment of tumor-bearing mice shows T-cell-dependent antitumor efficacy. MAP4K1 inhibition in conjunction with PD-L1 blockade results in a superior antitumor impact, illustrating the complementarity of the single agent treatments.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure–Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo 通过结构-活性关系研究发现高水溶性和生物相容性环葫芦[n]脲 FY-3451 是一种通用拮抗剂，可快速逆转体内的神经肌肉阻滞剂

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-26 DOI: 10.1021/acs.jmedchem.4c01960

Ke Feng, Yue-Yang Liu, Yang Zong, Zhuo Lei, Yan Wu, Jingyu Yang, Furong Lin, Qiao-Yan Qi, Qian Li, Sheng-Yi Zhuang, Jiangshan Zhang, Jia Tian, Wei Zhou, Da Ma, Dan-Wei Zhang, Zhan-Ting Li, Shang-Bo Yu

{"title":"Structure–Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo","authors":"Ke Feng, Yue-Yang Liu, Yang Zong, Zhuo Lei, Yan Wu, Jingyu Yang, Furong Lin, Qiao-Yan Qi, Qian Li, Sheng-Yi Zhuang, Jiangshan Zhang, Jia Tian, Wei Zhou, Da Ma, Dan-Wei Zhang, Zhan-Ting Li, Shang-Bo Yu","doi":"10.1021/acs.jmedchem.4c01960","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01960","url":null,"abstract":"The development of a reversal agent that can rapidly reverse clinically used nondepolarizing neuromuscular blocking agents (NMBAs) has long been a challenge. Here, we report the synthesis of a series of highly water-soluble acyclic cucurbit[n]urils (acCBs). Systematic structure–activity relationship studies reveal that introducing two propylidene units on the peripheral benzene rings not only remarkably improves the activity of the corresponding derivative acCB6 (FY 3451) in reversing the neuromuscular block of rocuronium, cisatracurium, vecuronium, and pancuronium, the four clinically used NMBAs, through stable inclusion, but also allows for high water-solubility as well as a maximum tolerated dose (2000 mg/kg on rats). In vivo experiments with rats show that, at the identical dose of 25 mg/kg, for rocuronium, vecuronium, and pancuronium, acCB6 can achieve a recovery time shorter than that of sugammadex for rocuronium and, at the dose of 100 mg/kg, realize comparably rapid reversal for cisatracurium.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Toward the Design of Allosteric Effectors: Gaining Comprehensive Control of Drug Properties and Actions 设计异构效应物质：全面控制药物特性和作用

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-26 DOI: 10.1021/acs.jmedchem.4c01043

Wei-Ven Tee, Sylvester J. M. Lim, Igor N. Berezovsky

{"title":"Toward the Design of Allosteric Effectors: Gaining Comprehensive Control of Drug Properties and Actions","authors":"Wei-Ven Tee, Sylvester J. M. Lim, Igor N. Berezovsky","doi":"10.1021/acs.jmedchem.4c01043","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01043","url":null,"abstract":"While the therapeutic potential of allosteric drugs is increasingly realized, the discovery of effectors is largely incidental. The rational design of allosteric effectors requires new state-of-the-art approaches to account for the distinct characteristics of allosteric ligands and their modes of action. We present a broadly applicable computational framework for obtaining allosteric site–effector pairs, providing targeted, highly specific, and tunable regulation to any functional site. We validated the framework using the main protease from SARS-CoV-2 and the K-RasG12D oncoprotein. High-throughput per-residue quantification of the energetics of allosteric signaling and effector binding revealed known drugs capable of inducing the required modulation upon binding. Starting from fragments of known well-characterized drugs, allosteric effectors and binding sites were designed and optimized simultaneously to achieve targeted and specific signaling to distinct functional sites, such as, for example, the switch regions of K-RasG12D. The generic framework proposed in this work will be instrumental in developing allosteric therapies aligned with a precision medicine approach.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and Optimization of a Series of Vinyl Sulfoximine-Based Analogues as Potent Nrf2 Activators for the Treatment of Multiple Sclerosis 发现并优化一系列乙烯基亚磺酰亚胺类似物，作为治疗多发性硬化症的强效 Nrf2 激活剂

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-26 DOI: 10.1021/acs.jmedchem.4c01907

Yoowon Kim, Jaehwan Kim, Byungeun Kim, Rium Kim, Hyeon Jeong Kim, Elijah Hwejin Lee, Jushin Kim, Jiwoo Park, Yeeun Jeong, Sang In Park, Hyemin Kim, Minsik Kang, Jaeick Lee, Yong-Sun Bahn, Ji Won Choi, Jong-Hyun Park, Ki Duk Park

{"title":"Discovery and Optimization of a Series of Vinyl Sulfoximine-Based Analogues as Potent Nrf2 Activators for the Treatment of Multiple Sclerosis","authors":"Yoowon Kim, Jaehwan Kim, Byungeun Kim, Rium Kim, Hyeon Jeong Kim, Elijah Hwejin Lee, Jushin Kim, Jiwoo Park, Yeeun Jeong, Sang In Park, Hyemin Kim, Minsik Kang, Jaeick Lee, Yong-Sun Bahn, Ji Won Choi, Jong-Hyun Park, Ki Duk Park","doi":"10.1021/acs.jmedchem.4c01907","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01907","url":null,"abstract":"Multiple sclerosis (MS) is an immune-mediated neurodegenerative disease of the central nervous system (CNS), which leads to demyelination, axonal loss, and neurodegeneration. Increased oxidative stress and neurodegeneration have been implicated in all stages of MS, making neuroprotective therapeutics a promising strategy for its treatment. We previously have reported vinyl sulfones with antioxidative and anti-inflammatory properties that activate nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that induces the expression of cytoprotective genes against oxidative stress. In this study, we synthesized vinyl sulfoximine derivatives by modifying the core structure and determined therapeutic potential as Nrf2 activators. Among them, 10v effectively activated Nrf2 (EC50 = 83.5 nM) and exhibited favorable drug-like properties. 10v successfully induced expression of Nrf2-dependent antioxidant enzymes and suppressed lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells. We also confirmed that 10v effectively reversed disease progression and attenuated demyelination in an experimental autoimmune encephalitis (EAE) mouse model of MS.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids 合成对结直肠癌有显著疗效的 LSD1/HDAC 抑制剂：体外和体内研究，包括患者生成的器官组织

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01098

Po-Yu Chou, Mei-Jung Lai, Kelvin K. Tsai, Li-Hsin Cheng, Yi-Wen Wu, Mei-Chuan Chen, Shiow-Lin Pan, Hsiu-O Ho, Kunal Nepali, Jing-Ping Liou

{"title":"Syntheses of LSD1/HDAC Inhibitors with Demonstrated Efficacy against Colorectal Cancer: In Vitro and In Vivo Studies Including Patient-Derived Organoids","authors":"Po-Yu Chou, Mei-Jung Lai, Kelvin K. Tsai, Li-Hsin Cheng, Yi-Wen Wu, Mei-Chuan Chen, Shiow-Lin Pan, Hsiu-O Ho, Kunal Nepali, Jing-Ping Liou","doi":"10.1021/acs.jmedchem.4c01098","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01098","url":null,"abstract":"Precedential evidence ascertaining the overexpression of LSD1 and HDACs in colorectal cancer spurred us to design a series of dual LSD1-HDAC inhibitors. Capitalizing on the modular nature of the three-component HDAC inhibitory model, tranylcypromine as a surface recognition motif was appended to zinc-binding motifs via diverse linkers. A compendium of hydroxamic acids was generated and evaluated for in vitro cytotoxicity against HCT-116 cells (human colorectal cancer cell lines). The most potent cell growth inhibitor 2 (GI50 = 0.495 μMm HCT-116 cells) shows promising anticancer effects by reducing colony formation and inducing cell cycle arrest in HCT-116 cells. It exhibits preferential inhibition of HDAC6, along with potent inhibition of LSD1 compared to standard inhibitors. Moreover, Compound 2 upregulates acetyl-tubulin, acetyl-histone H3, and H3K4me2, indicative of LSD1 and HDAC inhibition. In vivo, it demonstrates significant antitumor activity against colorectal cancer, better than irinotecan, and effectively inhibits growth in patient-derived CRC organoids.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

68Ga/177Lu-Labeled Theranostic Pair for Targeting Fibroblast Activation Protein with Improved Tumor Uptake and Retention 用于靶向成纤维细胞活化蛋白的 68Ga/177Lu 标记放射治疗对，可提高肿瘤吸收和保留率

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01812

Jiawen Huang, Xiaojun Zhang, Qingxing Liu, Fengping Gong, Yanchao Huang, Shun Huang, Lilan Fu, Ganghua Tang

{"title":"68Ga/177Lu-Labeled Theranostic Pair for Targeting Fibroblast Activation Protein with Improved Tumor Uptake and Retention","authors":"Jiawen Huang, Xiaojun Zhang, Qingxing Liu, Fengping Gong, Yanchao Huang, Shun Huang, Lilan Fu, Ganghua Tang","doi":"10.1021/acs.jmedchem.4c01812","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01812","url":null,"abstract":"Fibroblast activation protein (FAP) is specifically expressed on cancer-associated fibroblasts in over 90% of tumors and is considered a promising target for cancer theranostics. Here, we developed a novel tracer, DOTA-FAPT, and labeled it with gallium-68 and lutetium-177 as a theranostic pair. [68Ga]Ga/[177Lu]Lu-FAPT exhibited high stability and hydrophilicity, as well as strong affinity to the FAP target. Micro-PET/CT imaging revealed that [68Ga]Ga-FAPT exhibited significantly increased uptake in tumors and extended retention in A549-FAP and U87MG tumor xenografts as compared to [68Ga]Ga-FAPI-04, demonstrating favorable pharmacokinetic characteristics in vivo. Therapeutic studies showed that [177Lu]Lu-FAPT had higher tumor accumulation compared to [177Lu]Lu-FAPI-04, leading to stronger tumor growth inhibition. The first-in-human evaluation also revealed that [68Ga]Ga-FAPT has good in vivo distribution and superior diagnostic efficacy on primary and lymph node metastases in a patient with lung cancer. Our encouraging results suggest that 68Ga/177Lu-labeled DOTA-FAPT is a theranostic pair with broad application prospect.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Design, Synthesis, and Biological Evaluation of Covalently Mucoadhesive Derivatives as Nonsystemic Intestine-Targeted TGR5 Agonists 作为非系统性肠靶向 TGR5 激动剂的共价黏附性衍生物的设计、合成和生物学评价

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01637

Shizhen Zhao, Le Wang, Xiaotong Huang, Yali Xiao, Mengqi Li, Xueyuan Huang, Xueyu Chen, Shengjie Li, Jing Xie, Peng Liu, Yan-Dong Wang, Wei-Dong Chen

{"title":"Design, Synthesis, and Biological Evaluation of Covalently Mucoadhesive Derivatives as Nonsystemic Intestine-Targeted TGR5 Agonists","authors":"Shizhen Zhao, Le Wang, Xiaotong Huang, Yali Xiao, Mengqi Li, Xueyuan Huang, Xueyu Chen, Shengjie Li, Jing Xie, Peng Liu, Yan-Dong Wang, Wei-Dong Chen","doi":"10.1021/acs.jmedchem.4c01637","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01637","url":null,"abstract":"Takeda G-protein-coupled receptor 5 (TGR5) is considered a promising therapeutic target for treating type 2 diabetes mellitus (T2DM), obesity, and other metabolism-related diseases. Although many TGR5 agonists have been identified, they might cause some side effects in the gallbladder and the heart. To reduce these side effects and improve glucose-lowering capability, we first designed and synthesized a series of 4-phenoxynicotinamide intestine-targeted TGR5 agonist derivatives containing maleimides in the side chains with different linker lengths. All of the target compounds demonstrated significant TGR5 agonistic activity, among which compound 22b displayed the best TGR5 agonistic activity. Additionally, compound 22b displayed low Caco-2 cell permeability and strong mucoadhesion to mucin and the rat intestine. In C57BL/6J, diet-induced obese, and db/db mice, compound 22b demonstrated a robust and prolonged hypoglycemic effect along with an acceptable safety profile.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Assessing Darkness of the Human Kinome from a Medicinal Chemistry Perspective 从药物化学角度评估人类运动基因组的黑暗程度

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01992

Selina Voßen, Elena Xerxa, Jürgen Bajorath

引用次数: 0

Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma 发现新型 PROTAC SIRT6 降解剂，对肝细胞癌具有强大疗效

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01223

Jinbo Huang, Jiajie Su, Haiyu Wang, Jiayi Chen, Yuan Tian, Jun Zhang, Tingting Feng, Longjiang Di, Xiaopeng Lu, Hao Sheng, Qian Zhu, Xinyun Chen, Jingchao Wang, Xingkai He, Yerkezhan Yerkinkazhina, Zhongyi Xie, Yuxin Shu, Tianshu Kang, Huangqi Tang, Jinqin Qian, Wei-Guo Zhu

{"title":"Discovery of Novel PROTAC SIRT6 Degraders with Potent Efficacy against Hepatocellular Carcinoma","authors":"Jinbo Huang, Jiajie Su, Haiyu Wang, Jiayi Chen, Yuan Tian, Jun Zhang, Tingting Feng, Longjiang Di, Xiaopeng Lu, Hao Sheng, Qian Zhu, Xinyun Chen, Jingchao Wang, Xingkai He, Yerkezhan Yerkinkazhina, Zhongyi Xie, Yuxin Shu, Tianshu Kang, Huangqi Tang, Jinqin Qian, Wei-Guo Zhu","doi":"10.1021/acs.jmedchem.4c01223","DOIUrl":"https://doi.org/10.1021/acs.jmedchem.4c01223","url":null,"abstract":"Sirtuin 6 (SIRT6), a member of the SIRT family, plays essential roles in the regulation of metabolism, inflammation, aging, DNA repair, and cancer development, making it a promising anticancer drug target. Herein, we present our use of proteolysis-targeting chimera (PROTAC) technology to formulate a series of highly potent and selective SIRT6 degraders. One of the degraders, SZU-B6, induced the near-complete degradation of SIRT6 in both SK-HEP-1 and Huh-7 cell lines and more potently inhibited hepatocellular carcinoma (HCC) cell proliferation than the parental inhibitors. In preliminary mechanistic studies, SZU-B6 hampered DNA damage repair, promoting the cellular radiosensitization of cancer cells. Our SIRT6 degrader SZU-B6 displayed promising antitumor activity, particularly when combined with the well-known kinase inhibitor sorafenib or irradiation in an SK-HEP-1 xenograft mouse model. Our results suggest that these PROTACs might constitute a potent therapeutic strategy for HCC.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

First Demonstration of In Vivo PDE11A4 Target Engagement for Potential Treatment of Age-Related Memory Disorders 首次展示体内 PDE11A4 靶点参与治疗老年性记忆障碍的潜力

IF 7.3 1区医学

Journal of Medicinal Chemistry Pub Date : 2024-09-25 DOI: 10.1021/acs.jmedchem.4c01794

Shams ul Mahmood, Jeremy Eberhard, Charles S. Hoffman, Dennis Colussi, John Gordon, Wayne Childers, Elvis Amurrio, Janvi Patel, Michy P. Kelly, David P. Rotella

引用次数: 0