Discovery of an Androgen Receptor Degrader Featuring a Pyridazinyl Glutarimide CRBN-Binding Motif for Transdermal Treatment of Androgenetic Alopecia [0.03%]
一种用于雄激素性脱发经皮治疗的新型andrar配体(pygdz)，通过降解雄激素受体发挥作用
Xiao Wang,Ling Ge,Yawei Yu et al.
Xiao Wang et al.
Androgenetic alopecia (AGA) is primarily driven by overexpression of androgen receptor (AR) in hair follicles, leading to androgen hypersensitivity and progressive follicular miniaturization. Although PROTAC degraders offer the potential fo...
Developing Predictive Models by Sharing Predictions - An Investigation of a Federated Learning Approach for ADMET Predictions [0.03%]
通过共享预测来开发预测模型——一种用于ADMET预测的联邦学习方法研究
Rajarshi Guha,Wenyi Wang,Edward Price et al.
Rajarshi Guha et al.
Machine learning models for ADMET prediction benefit from large, diverse data sets, yet such data are typically siloed across organizations. Federated learning (FL) enables collaborative modeling while preserving data privacy. Here, we inve...
Macrophage-Centric Phenotypic Screening Identifies Tetrazolone-Based HDAC6 Inhibitors That Reprogram the Tumor Immune Microenvironment and Improve Immune Checkpoint Blockade [0.03%]
以巨噬细胞为中心的表型筛选发现了基于四氮唑的HDAC6抑制剂，可重塑肿瘤免疫微环境并改善免疫检查点阻断疗法
Nithya Gajendran,Manasa Suresh,Sebastian J Marquez R et al.
Nithya Gajendran et al.
Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment (TME) and influencing the outcomes of immunotherapy. However, most drug screening strategies emphasize tumor cell cytotoxicity and neglect immune ...
Structure-Guided Grafting of Cell-Penetrating Motifs into Stapled Peptides for Intracellular PPI Inhibition [0.03%]
基于结构的细胞膜穿透位点嵌合肽的设计合成及活性研究
Minami Fujita,Tsuyoshi Konuma,Ayaka Yoshida et al.
Minami Fujita et al.
Protein-protein interactions (PPIs) are promising drug targets, yet peptide modulation of intracellular PPIs is limited by poor membrane permeability. Although conjugation with cell-penetrating peptides (CPPs) improves delivery, it often in...
Prophylactic Active Immunization Protects against Xylazine-Induced Pharmacological Effects in Rats [0.03%]
预防性主动免疫可保护大鼠免受交叉净诱导的药理学效应的影响
Caroline M Kim,Robert W Seaman Jr,Courtney Marecki et al.
Caroline M Kim et al.
Opioid-related overdoses have continued to rise in the past decade and have been further exacerbated by polydrug exposure involving the α2 adrenergic receptor agonist xylazine, a veterinary tranquilizer referred to as "tranq" or "tranq dop...
Fluorinated Ultralong-Acting Neuromuscular Blocking Agent with Improved Activity Profile and Biosafety for the Development of Blockade and Reversal Partner Drugs [0.03%]
具有改良药代动力学特性和生物安全性的超长效神经肌肉阻滞剂氟化合物及其拮抗剂药物组合的开发研究
Shi-Xian Gan,Ru-Lei Zhang,Congying Guo et al.
Shi-Xian Gan et al.
Halogenation has been used as a useful strategy to optimize an imidazolium-based macrocyclic ultralong-acting neuromuscular blocking agent for improved bioactivity and biocompatibility. A structure-activity relationship study for 18 compoun...
Structure-Guided Designed [18F]-labeled FAPI for Enhanced Hydrophilicity: From Preclinical to First-In-Human Study [0.03%]
基于结构导向设计的[18F]标记FAPI衍生物：从增强亲水性到临床试验
Xingyu Mu,Lei Zhang,Zihao Chen et al.
Xingyu Mu et al.
Fibroblast activation protein (FAP) is highly expressed in cancer-associated fibroblasts and represents an attractive target for PET imaging. Here, we report [18F]AlF-NOTA-GL01, an improved FAPI-46 derivative bearing an N-methyl-benzenesulf...
Discovery of Selective Inhibitors for β-Actin Polymerization as Potential Anticancer Agents In Vitro and In Vivo [0.03%]
体内外发现β-actin聚合选择性抑制剂作为潜在的抗肿瘤制剂
Weixiong Chen,Shilong Hao,Donghui Sun et al.
Weixiong Chen et al.
No selective actin inhibitor has been developed due to the high homology of actin isoforms. Given the distributions of cysteine residues among actin isoforms, we propose the covalent small-molecule targeting approach offers a distinct path ...
Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens [0.03%]
设计不易被外排的抗生素以应对 multidrug-resistant病原体抗菌药物的研发困境
Mark Laws,Charlotte K Hind,Kazi Sharmin Nahar et al.
Mark Laws et al.
We report a novel Efflux Resistance Breaker (ERB) strategy for designing antibiotics intrinsically resistant to efflux, using fluoroquinolones as a model class. ERB-modified fluoroquinolones showed enhanced intracellular accumulation and ma...
Discovery of Novel Hsp90 Inhibitor-Evodiamine Derivative Conjugates as Potent and Orally Active Antitumor Agents for Colon Cancer Therapy [0.03%]
新型Hsp90抑制剂-小檗胺衍生物连接体抗结肠肿瘤药物的发现与研究
Yuhang Sun,Keliang Li,Hua Sun et al.
Yuhang Sun et al.
Natural products (NPs) and their derivatives have long been important components of antitumor drugs. Nevertheless, traditional natural product derivatives are generally limited by tumor-targeting deficiency and toxicity to normal tissue. Pa...