Development and Preclinical Evaluation of the Novel Peptide-Based Tracer 68Ga-PDT01 for Noninvasive PET Imaging of PD-L1 Expression [0.03%]
新型肽基PD-L1显像剂68Ga-PDT01的开发和临床前评估
Cong Wang,Hange Yang,Xuegong Fan et al.
Cong Wang et al.
Programmed death-ligand 1 (PD-L1) is a key mediator of tumor immune evasion and plays a critical role in tumor immunodiagnosis and immunotherapy. We developed a PD-L1-targeted peptide PET tracer, 68Ga-PDT01, incorporating a 2-substituted na...
Integrating AI in Medicinal Chemistry for Accelerated Drug Discovery: A Comprehensive SAR (CSAR) Optimization Strategy and Discovery of Potent ALDH3A1 Inhibitors [0.03%]
人工智能在药物化学中的整合以加速药物发现：全面的结构活性关系(SAR)优化策略及醛脱氢酶3家族A1型（ALDH3A1）抑制剂的发现
Sankalp Jain,Adam Yasgar,Anu Dalal et al.
Sankalp Jain et al.
Developing potent, selective small-molecule inhibitors remains a major challenge in drug discovery. ALDH3A1, a detoxifying aldehyde dehydrogenase isoform implicated in cancer and neurodegeneration, is a promising yet underexplored therapeut...
A Rationally Engineered MAGL-Activatable Fluorogenic Probe Enables Efficient Discovery of Anti-Inflammatory and Hepatoprotective Agents [0.03%]
一种合理设计的能够激活MAGL的荧光探针可有效用于抗炎保肝药物的发现
Lele Liu,Shimin Hou,Lin Chen et al.
Lele Liu et al.
Targeted inhibition of monoacylglycerol lipase (MAGL) represents a promising therapeutic strategy for inflammatory diseases and drug-induced hepatotoxicity. However, the lack of robust screening assays hindered the efficient discovery of po...
Discovery of a Biased Kelch-like ECH-Associated Protein 1-p62 (Keap1-p62) Protein-Protein Interaction (PPI) Inhibitor for the Management of p62 Aberrant Hepatocellular Carcinoma [0.03%]
发现一种偏向性的Kelch-likeECH相关蛋白1-p62（Keap1-p62）蛋白质-蛋白质相互作用（PPI）抑制剂以治疗p62异常的肝细胞癌
Ziquan Zhao,Hongjin Lu,Jinshen Zhang et al.
Ziquan Zhao et al.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pleiotropic transcription factor essential for cellular defense. Extensive research has demonstrated its oncogenic role, positioning Nrf2 as a promising target for cancer therapy. Howe...
From Scaffold Optimization to a Promising Lead: Discovery of a Novel Roemerine Analogue, a Multichannel Antiarrhythmic with Low hERG Liability and Functional Restoration Capacity [0.03%]
从先导优化到临床候选化合物：新型紫草素类似物的发现，一种多通道抗心律失常药物，具有低心脏毒性和功能性恢复能力
Zhanpan Wu,Wenping Wang,Chunyan Yang et al.
Zhanpan Wu et al.
This study identified 6-24, a novel antiarrhythmic lead derived from the roemerine scaffold, which exhibited a distinctive multichannel blockade profile targeting Nav1.5 and Cav1.2, while demonstrating only weak inhibition of hERG. This gen...
Discovery of a Potent, Selective and In Vivo Active Aurora A PROTAC Degrader from a Promiscuous Kinase Inhibitor [0.03%]
一种具有体内活性的 aurka 靶向蛋白降解剂(protar)化合物的设计及其应用
Yulin Mao,Meiying Zhang,Hao Tang et al.
Yulin Mao et al.
Discovering novel kinase modulators that combine high selectivity with the ability to regulate noncatalytic functions remains a crucial goal in kinase drug discovery. Here, we use Aurora A as a case study to demonstrate that proteolysis-tar...
Discovery of a Novel Potent and Orally Efficacious PGK1 Inhibitor C67-47 for the Treatment of Human Pancreatic Cancer [0.03%]
一种新型有效的PGK1抑制剂C67-47用于人类胰腺癌治疗的发现
Lihua Liu,Xiaoming Jiang,Hong Zhao et al.
Lihua Liu et al.
Phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in glycolysis, is frequently overexpressed in a wide range of human malignancies. Beyond its canonical glycolytic function, PGK1 also functions as a protein kinase playing a ...
Harnessing the Quinoline Scaffold toward Discovery and Development of Antimalarials [0.03%]
喹啉骨架的利用促进新型抗疟药物的研发
Guang Huang,Yu Yuan
Guang Huang
The quinoline scaffold, a well-established privileged structure, continues to play a central role in antimalarial drug discovery. This perspective presents a comprehensive summary and discussion of the antimalarial targets of quinoline deri...
Discovery and Optimization of IRBM-Z-2, an Allosteric Zika Virus NS2B-NS3 Protease Inhibitor Exhibiting In Vivo Efficacy [0.03%]
一种具有体内疗效的寨卡病毒NS2B-NS3蛋白酶变构抑制剂IRBM-Z-2的发现与优化
Esther Torrente,Antonio Quotadamo,Alessandra Corio et al.
Esther Torrente et al.
Zika virus is an increasing medical and socio-economic burden in (sub)tropical regions, with no effective treatments available. Previously, we identified a novel series of N-carbamoylsydnone imine derivatives as potent ZIKV NS2B-NS3 proteas...
Structural Optimization of NET-Targeted Agents: ortho-Radioiodinated Phenoxyalkylguanidine Achieves Enhanced Tumor Retention and Radiotherapeutic Efficacy [0.03%]
NET导向放射性治疗药物的结构优化：邻位放射性标记的芳氧烷基胍实现肿瘤组织滞留和放疗效果增强
Xijian Chen,Lili Pan,Yueqi Wang et al.
Xijian Chen et al.
The norepinephrine transporter (NET) represents a validated target for theranostics in neuroendocrine tumors, yet clinical agents such as [123I]/[131I]mIBG exhibit suboptimal tumor retention, deiodination, and dose-limiting toxicity. To add...