Development of TSSK1 and TSSK2 Targeted Degraders Reveals Sperm Machinery for Protein Degradation and Potential for Nonhormonal Male Contraception [0.03%]
靶向TSSK1和TSSK2的降解剂的研发揭示了精子的蛋白质降解机制及潜在的非激素类男性避孕方法
Jerrett A Holdaway,Lokesh Saini,Raven Coil-Otto et al.
Jerrett A Holdaway et al.
We report the design, synthesis, and characterization of a series of targeted degraders directed against testis-specific serine/threonine kinases TSSK1 and TSSK2. A stable CHO-K1 cell line expressing HiBiT-tagged TSSK1 enabled quantitative ...
MEG-mod: A Multiview Enhanced Graph Neural Network for Knockdown Efficiency Prediction of Chemically Modified siRNA [0.03%]
基于多视图增强图神经网络的化学修饰siRNA敲除效率预测模型研究
Yuanting Chen,Mengyu Tong,Long Chen et al.
Yuanting Chen et al.
Chemical modification is essential for improving the stability and knockdown efficiency of siRNAs. However, the combinatorial complexity of modification types and positions makes rational design difficult. Here, we propose MEG-mod, a deep l...
Structure-Guided Optimization of Novel Inhibitors of Plasmodium Lysyl-tRNA Synthetase with Multistage Activity against Malaria Parasites [0.03%]
以纤细藤黄素为先导结构的抗疟药物Plasmodium lysyl-tRNA合成酶新型抑制剂的优化研究
Barbara Forte,Fiona Bellany,Peter S Campbell et al.
Barbara Forte et al.
A fused dihydropyrrolidino-pyrimidine hit with low lipophilicity and excellent ligand efficiency was identified in a biochemical screen of the Global Health Chemical Diversity Library (GHCDL) against Plasmodium lysyl-tRNA synthetase (KRS). ...
Evolving Strategies for Previously Drugged Therapeutic Targets: Medicinal Chemistry Insights from Paradigmatic Cases [0.03%]
以往药物研发靶点的进化策略：范例情况的药物化学见解
Yujun Deng,Shouwei Wang,Lei Geng et al.
Yujun Deng et al.
Previously drugged therapeutic targets have continued to attract substantial scientific and clinical interest, resulting in numerous FDA approvals for new chemical entities (NCEs) over the past 15 years. This sustained productivity demonstr...
Bisbenzoselenophene[ b]-Fused AzaBODIPYs as Strong Near-Infrared-Absorbing Photosensitizers for Effective Photodynamic Tumor Therapy [0.03%]
有效的光动力肿瘤治疗的强近红外吸收型光敏剂：并环氮杂BODIPY类化合物bisbenzoselenophene[ b] fused azaBODIPYs
Ziyu Zhang,Yuqi Xie,Qinghua Wu et al.
Ziyu Zhang et al.
Photodynamic therapy (PDT) is a promising precision treatment for cancer, yet its clinical translation is often hindered by the lack of near-infrared (NIR) photosensitizers that simultaneously offer efficient reactive oxygen species (ROS) g...
Cationic Photosensitizer-Functionalized Bacteria for Targeted Photothermal-Photodynamic Therapy with Immune Activation [0.03%]
阳离子光敏剂功能化细菌诱导精准光热/免疫治疗
Ling Lei,Junyi Liu,Yang Liu et al.
Ling Lei et al.
Bacteria possess innate tumor tropism and immunostimulatory properties, yet their efficacy as monotherapy is limited. Here, we report rational cationic interface engineering of bacteria through a tricationic heptamethine photosensitizer (Cy...
Discovery of Novel Thiazolo[4,5- d]pyrimidin-7(6 H)-Ones as Extrasynaptic δ-GABAA Receptor-Preferring PAMs with Rapid Antidepressant-like Efficacy [0.03%]
一类新型噻唑并[4,5-d]嘧啶酮类化合物作为外突触δ- GABA受体偏好性正向别构调节剂具有快速抗抑郁样作用的发现
Han Wang,Weiming Liao,Yunzhe Li et al.
Han Wang et al.
Activation of extrasynaptic δ-GABAARs represents a promising strategy for rapid-acting antidepressant therapy in major depressive disorder (MDD). Here, we report the discovery and pharmacological characterization of a novel series of thiaz...
C-BODIPY Dyads Based on Fused-Ring Organoboron Scaffolds for Efficient Photodynamic Therapy Targeting Candida albicans Yeast and Biofilms [0.03%]
基于稠环有机硼骨架的C-BODIPY偶联物高效靶向白色念珠菌芽生孢子和 biofilm 光动力治疗研究
Karolina A Urbanowicz,Paulina H Marek-Urban,Karolina Wrochna et al.
Karolina A Urbanowicz et al.
A series of heavy-atom-free C-BODIPY photosensitizers based on five different types of fused-ring organoboron scaffolds was designed for the application in antifungal photodynamic therapy. The dyes were functionalized with a positively char...
Structural Modification and Development of N-(1,2,3,4-Tetrahydro-3-isoquinolinylmethyl)benzamide, BPR1M492, as a Potent and Rapid-Onset Opioid Analgesic with Reduced Withdrawal Symptoms [0.03%]
N-(1,2,3,4-四氢-3-喹啉甲基)苯胺BPR1M492的结构修饰及开发成一种起效快、镇痛作用强且戒断症状减少的阿片受体调节剂
Po-Wei Chang,Yung-Chiao Chang,Ya-Wen Tien et al.
Po-Wei Chang et al.
A series of N-(1,2,3,4-tetrahydro-3-isoquinolinylmethyl)benzamides, which are potent μ-opioid receptor (MOR) agonists, has been discovered. The most promising compound, compound 56 (BPR1M492), is an MOR agonist without a clear signaling bi...
Discovery of YTB53, a Marine-Derived MNK-Active Anti-Acute Myeloid Leukemia Lead with Multi-Kinase Activity [0.03%]
海洋来源的MNK活性抗急性髓系白血病先导化合物YTB53及其多激酶活性发现
Xiang Chen,Liting Zhang,Yuqiang Han et al.
Xiang Chen et al.
Acute myeloid leukemia (AML) remains a therapeutic challenge due to its aggressive nature and poor prognosis in relapsed/refractory cases. This study explores novel MNK (MAP kinase-interacting kinase) inhibitors derived from the marine natu...