Design, Synthesis, and Antitubercular Activity Evaluation of Novel Nitroimidazole Derivatives [0.03%]
新型硝基咪唑衍生物的设计、合成及抗结核活性评价
Guoquan Wan,Yan Chen,Xiaorui Zhang et al.
Guoquan Wan et al.
The development of novel antitubercular agents represents a critical strategy against drug-resistant tuberculosis (TB). In this study, we designed and synthesized a series of novel nitroimidazole derivatives from Delemanid by introducing an...
SHP2 Inhibition Reveals Compensatory PI3K-AKT Activation in KRAS-Driven Pancreatic Cancer: Discovery of SDUY104 and Rational Approaches for Combination Therapy [0.03%]
SHP2抑制揭示KRAS驱动的胰腺癌中PI3K-AKT补偿性激活：SDUY104的发现及联合治疗的理性策略
Chengchun Zhu,Chen Wang,Yijie Zhu et al.
Chengchun Zhu et al.
Pancreatic cancer remains one of the most lethal malignancies with numerous patients harboring KRAS mutations. Herein, we developed a series of furanyl amide-based SHP2 allosteric inhibitors through optimization of our in-house lead compoun...
Beyond Target Occupancy in Triple-Negative Breast Cancer: A Medicinal Chemistry Perspective on Modality-Guided Design for Durable Network Control [0.03%]
超越靶点 occupancy：从药物化学角度探讨模态引导设计在三阴性乳腺癌中的持久网络控制作用
Weikun Zeng,Yihua Chen,Nouri Neamati et al.
Weikun Zeng et al.
Triple-negative breast cancer (TNBC) remains difficult to treat because durable response is rarely achieved with conventional occupancy-driven inhibition. The central challenge is not simply a lack of actionable targets but a mismatch betwe...
PROTAC-Mediated DPP-4 Degradation: A New Solution for Type 2 Diabetes [0.03%]
用于二型糖尿病治疗的DPP-4降解的新方案(PROTAC技术)
Wei Zeng,Liangzhu Feng
Wei Zeng
Dipeptidyl peptidase-4 (DPP-4) is an important aggravating factor in the progression and exacerbation of type 2 diabetes mellitus (T2DM), a condition characterized by diminished insulin responsiveness because it rapidly degrades glucagon-li...
Drug Delivery Strategy Exploiting Amino Acid Prodrugs: Improving Oral Bioavailability and Overcoming Nonlinear Pharmacokinetic Challenges Following Dose Escalation of a CK2 Inhibitor with Poor Solubility [0.03%]
利用氨基酸前药改善口服生物利用度并克服CK2抑制剂给药剂量递增后的非线性药代动力学问题策略研究
Murugaiah A M Subbaiah,Thangeswaran Ramar,Mathiazhagan Annadurai et al.
Murugaiah A M Subbaiah et al.
Dissolution-limited absorption remains a major barrier to oral delivery of kinase inhibitors. BMS-135, a potent pan-CK2 inhibitor with robust antitumor efficacy, exhibited poor aqueous solubility (
Structure-Based Design and Optimization of Novel, Potent and Selective Covalent FGFR2/3 Inhibitors with a Tricyclic Core [0.03%]
基于结构的新型强效选择性共价FGFR2/3抑制剂（三环核心）的设计与优化
Xuzhi Lu,Zhaodi Tian,Xueqiang Li et al.
Xuzhi Lu et al.
Fibroblast growth factor receptors 2 and 3 (FGFR2/3) are attractive therapeutic targets in multiple human cancers. Here, we report the discovery of a series of tricyclic 1-(4-amino-5-ethynyl-8,9-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyrim...
Synthesis and Preclinical Evaluation of Structurally Optimized 68Ga-Labeled CXCR4 Radiotracers for PET Imaging of Atherosclerotic Plaque Inflammation [0.03%]
优化的放射性标记CXCR4示踪剂的合成及临床前评价用于动脉粥样硬化斑块炎症的PET分子显像研究
Jinglin Zhang,Ning Wang,Yuze Ma et al.
Jinglin Zhang et al.
Atherosclerosis is now widely recognized as a chronic inflammatory condition driven by the recruitment of leukocytes, with CXCR4 playing a critical role in plaque inflammation and disease progression. In this study, we report the developmen...
Hit-to-Lead Optimization of Energy-Coupling Factor (ECF) Transporter Inhibitors as Novel Antibiotic [0.03%]
能量耦合因子转运抑制剂作为新型抗生素的先导优化研究
Ioulia Exapicheidou,Aleksei Tsarenko,Lena Zeller et al.
Ioulia Exapicheidou et al.
Multiparameter optimization of a previously identified class of inhibitors of the energy-coupling factor (ECF) transporters enabled the confirmation of in vivo efficacy. ECFs are a class of transmembrane proteins that play a vital role in t...
Development and Biological Characterization of Fluorescent Dynorphins for the Visualization of Kappa Opioid Receptors [0.03%]
荧光_dynorphin_的开发及生物特性分析在κ-阿片受体可视化中的应用
Predrag Kalaba,Monika Perisic Böhm,Filip D̵ikić et al.
Predrag Kalaba et al.
The kappa opioid receptor (KOR) controls a wide variety of biological processes, including pain and reward responses. However, its precise spatiotemporal location remains poorly understood due to limited selective molecular tools. We addres...
Discovery of Highly Potent and Selective SOS1 Inhibitors for the Treatment of KRAS-Driven Colorectal Cancer [0.03%]
高效特异性SOS1抑制剂的发现及其在KRAS驱动型结直肠癌治疗中的应用
Xingchen Liu,Yuzhou Xiao,Yanmei Zhou et al.
Xingchen Liu et al.
The guanine nucleotide exchange factor SOS1 has emerged as an attractive therapeutic target for various KRAS-driven tumors. Herein, we employed a structure-based drug design strategy to develop a series of novel quinazoline-derived molecule...