Radiotherapy Activates Drug-Drug Conjugates for Platinum-Based Combinational Chemotherapy [0.03%]
放疗激活药物偶联物用于基于铂的联合化疗
Siyong Shen,Qunfeng Fu,Yuchen Hu et al.
Siyong Shen et al.
Platinum-based combination chemotherapy is a standard first-line treatment for major cancers. However, its dose-limiting toxicity significantly compromises the clinical utility. Here, we established a radiotherapy-activated platinum(IV) pro...
Antibody-Mediated Delivery of BRM/BRG1 Protein Degraders Affords Strong Antitumor Efficacy in Multiple BRM-Dependent Non-Small Cell Lung Cancer Xenograft Models [0.03%]
抗BRM/BRG1蛋白降解物的抗体介导递送在多种BRM依赖性非小细胞肺癌异种移植模型中表现出强力抗肿瘤效果
Summer A Baker Dockrey,Pravin Chandra,Huifen Chen et al.
Summer A Baker Dockrey et al.
The synthesis and biological characterization of multiple degrader antibody conjugates (DACs) bearing a heterobifunctional VHL-dependent proteolysis targeting chimera (PROTAC) payload is described. The conjugated molecule (A515) potently an...
X-ray Crystallography-Guided Discovery of a Potent Dual-Pocket Competitive SIRT5 Inhibitor against Sepsis-Associated AKI [0.03%]
基于X射线衍射的SIRT5双结合位点竞争性抑制剂用于治疗脓毒症相关急性肾损伤
Yingying Jiang,Lina Yang,Rui Xiong et al.
Yingying Jiang et al.
Sepsis-associated acute kidney injury (AKI) management remains an unmet clinical need. SIRT5 inhibition shows renoprotective effects, suggesting its therapeutic potential. Using the cocrystal structure of SIRT5-lead compound 1, we rationall...
Discovery of LT-1339-553 as a Potent RIPK1 Inhibitor for Schistosomiasis-Induced Hepatic Fibrosis [0.03%]
LT-1339-553对血吸虫病诱导的肝纤维化RIPK1抑制剂的作用发现
Ju-Lu Lu,Qin-Di He,Yi-Han Yang et al.
Ju-Lu Lu et al.
Hepatic fibrosis, a key pathological driver of chronic liver disease progression, lacks effective targeted therapies. Receptor-interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic target. Herein, we developed a highly...
A Small-Molecule Drug Conjugate Targeting FAP Exhibits Potent Activity in Dogs with Spontaneous Tumors [0.03%]
一种靶向FAP的小分子药物偶联物在自发性肿瘤犬模型中表现出显著的药效
Andrea Galbiati,Paola Roccabianca,Silvia Dell&#x;Aere et al.
Andrea Galbiati et al.
Antibody-drug conjugates have transformed the treatment of cancer, yet their clinical utility can be limited by suboptimal tumor penetration, complex manufacturing, and safety concerns. Replacing antibodies with low-molecular-weight ligands...
Enzyme-Triggered Charge and Conformation Switching for Tumor-Selective Peptide-Drug Conjugates [0.03%]
基于酶促电荷和构象转换的肿瘤选择性肽药物偶联物
Jiaying Wei,Qipeng Yan,Xingyue Jiang et al.
Jiaying Wei et al.
Functionalizing anticancer drugs with activatable peptides offers a versatile strategy to achieve tumor-selective delivery while minimizing systemic toxicity. Here, we report a γ-glutamyltransferase (GGT)-responsive cell-penetrating peptid...
Real-Time NanoBRET Target Engagement Reveals Permeability-Activity Relationships in BET-Targeting Degraders [0.03%]
基于纳米生物发光共振能量转移的实时靶向 engagement 分析揭示了降解剂类小分子化合物的渗透活性关系
Alexander Engstrom,James D Vasta,Matthew B Robers et al.
Alexander Engstrom et al.
Membrane permeability is critical to the function of proteolysis targeting chimeras (PROTACs), yet common methods such as the parallel artificial membrane permeability assay (PAMPA) and Caco-2 transwell assays are limited by their experimen...
The New Delhi Metallo-β-lactamase-1 Covalent Inhibitors Derived from Cephalexin Effectively Reverse Meropenem Resistance [0.03%]
来 carb 四代头孢菌素衍生物有效逆转新德里金属-β-内酰胺酶对美罗培南的耐药性
Wandong Liu,Chenyu Liu,Yan Guo et al.
Wandong Liu et al.
New Delhi metallo-β-lactamase-1 (NDM-1) hydrolyzes carbapenems and most β-lactam antibiotics, posing a significant threat to global health and underscoring the urgent need for effective inhibitors. To address this unmet need, we designed ...
From Serendipity to Rationality: Expanding Druggability by Molecular Glue Discovery [0.03%]
从偶然性到理性：通过分子胶的发现扩大可成药性范围
David E Heppner,Congbao Kang,Weijun Xu
David E Heppner
Bridging the Gap between In Vitro and Intracellular: Systematic Analysis and Screening Optimization of Inconsistencies between Target Activity and Cellular-Level Activity [0.03%]
从体外到细胞内的药物筛选优化及系统评价体系研究
Shujing Xu,Dazhou Shi,Mei Wang et al.
Shujing Xu et al.