Development of Novel Estradiol-Indole Hybrids Targeting SERT and ERβ as Potential Antidepressants [0.03%]
新型雌二醇-吲哚 hybrids针对SERT和ERβ的抗抑郁药物的研发
Chunyu Wu,Chunyu Gao,Guixing Fu et al.
Chunyu Wu et al.
Major depressive disorder (MDD) remains a global concern, with current treatments often showing delayed or limited efficacy. This research describes the development of novel estradiol-indole hybrids designed to inhibit the serotonin transpo...
MeLysine-Stapling Combined with N-Terminal Acetylation Yields Stable Oncolytic Peptides with Enhanced Antitumor Efficacy [0.03%]
组蛋白乙酰化模拟融合肽梅淋巴瘤裂解抗肿瘤机制研究
Lei Xu,Yi He,Xin Fan et al.
Lei Xu et al.
To overcome the proteolytic instability of oncolytic peptides, we developed a novel "MeLysine-stapling" strategy through intramolecular cross-linking of two α-methyl-substituted lysine residues. Applying this strategy to the cobra-derived ...
Discovery of Fosigotifator, a Potent eIF2B Activator with Desired Properties for Human Studies [0.03%]
新型TORC1激活剂Fosigotifator可有效改善小鼠模型的进行性肾脏疾病和神经退行性疾病症状
Jennifer M Frost,Yunsong Tong,Xiangdong Xu et al.
Jennifer M Frost et al.
The integrated stress response (ISR) is a highly conserved cellular pathway triggered by a variety of insults, reducing protein synthesis and inducing ATF4, leading to broadly remodeling the cellular transcriptome and metabolome. ISRIB, 1, ...
Identification of the Piperidyl Urea Derivative BAY-439 as a Potent and Selective Inhibitor of Human Phospholipase A2 Group V (hPLA2-G5) for the Treatment of Inflammatory Pain [0.03%]
人溶血磷脂酸合酶II低微变体的发现及其对奥沙利铂诱导的家兔神经毒性的治疗作用
Gernot Langer,Nico Bräuer,Daryl Walter et al.
Gernot Langer et al.
Human Phospholipase A2 Group V (hPLA2-G5) is elevated in inflammatory conditions and promotes neutrophil and macrophage recruitment. Its enzymatic activity activates lipid receptors and cytosolic phospholipase A2 (cPLA2), leading to arachid...
ABRefine: An Accurate Antibody Structure Refinement Method by Equivariant Graph Transformer with Rigid Body Constraint [0.03%]
基于等变图变换器和刚体约束的准确抗体结构优化方法
Jinxian Wang,Ziqiao Zhang,Xiaoyang Jing et al.
Jinxian Wang et al.
Accurate antibody structural modeling is essential for therapeutic antibody development. However, even advanced artificial intelligence models such as AlphaFold2/3 struggle to precisely predict antibody structures due to the high flexibilit...
Amping Up Receptor Balance and Bias: Fine Tuning of Unimolecular Multiagonists [0.03%]
通过单分子多激动剂精细调节受体平衡和偏向性
Damla Sürmeli,Kathleen M Sicinski,Tristan C Dinsmore et al.
Damla Sürmeli et al.
Unimolecular multiagonists integrating GLP-1R/GIPR, and increasingly GCGR agonism, have altered the landscape of peptide therapeutics for metabolic syndrome. This progress has shifted the field from optimizing individual ligands to engineer...
Discovery of a Novel Lung-Restricted ALK5 Inhibitor for the Treatment of Idiopathic Pulmonary Fibrosis [0.03%]
一种新型肺特异性ALK5抑制剂用于治疗特发性肺纤维化的新发现
Paolo Ronchi,Daniela Pizzirani,Daniele Pala et al.
Paolo Ronchi et al.
As part of a therapeutic approach to idiopathic pulmonary fibrosis (IPF) using inhaled ALK5 inhibitors, which enable targeted lung delivery while minimizing systemic side effects, this work describes the optimization process of a previously...
The Discovery of TNG456: A Highly Potent, Selective, Brain-Penetrant MTA-Cooperative PRMT5 Inhibitor for the Treatment of MTAP-Deleted Cancers [0.03%]
TNG456的发现：一种高效、选择性、能透过血脑屏障并与甲硫腺苷磷酸化酶共作用的蛋白精氨酸甲基转移酶5抑制剂，用于治疗甲硫腺苷磷酸化酶基因缺失型癌症
Kevin M Cottrell,Kimberly J Briggs,Alice Tsai et al.
Kevin M Cottrell et al.
Homozygous deletion of the methylthioadenosine phosphorylase (MTAP) gene occurs in 10-15% of all human cancers and up to 50% of high-grade malignant gliomas, representing one of the largest opportunities for precision oncology. Loss of MTAP...
Self-Dimerization Induced Proximity Targeting Chimeras (SDIPTAC) Lead to DCAF1 Loss of Function and Inhibition of HIV Replication [0.03%]
自二聚作用诱导的邻近标记嵌合体(SDIPTAC)导致DCAF1失活并抑制HIV复制
Mark F Mabanglo,Smriti Srivastava,Yusuke Matsui et al.
Mark F Mabanglo et al.
DCAF1 is a donut shaped WD40 repeat protein and a substrate receptor of two distinct E3 ligases. In HIV-1 infection, the viral protein Vpr binds to the top surface of DCAF1, changes its substrate specificity to degrade human proteins involv...
Discovery of CZL-149: A Novel, Highly Potent, and Orally Bioavailable Dual Inhibitor Targeting BET and p300/CBP Bromodomains with Strong Antitumor Efficacy [0.03%]
CZL-149的发现：一种新型高效口服生物可利用的BET和p300/CBP溴结构域双靶点抑制剂及其显著的抗肿瘤活性
Zonglong Chen,Qiongyu Shi,Yan Zhang et al.
Zonglong Chen et al.
Dual inhibition of bromodomain and extra terminal (BET) and E1A-binding protein (p300)/CREB-binding protein (CBP) bromodomains has shown superior antiproliferative activity compared to selectively targeting either family alone. Despite this...