Discovery of azaindole/indole-fused pyrimidine tetracyclic scaffolds as novel potent CDK7 inhibitors [0.03%]
新型 potency CDK7抑制剂的aza-indole/indole拼杂嘧啶四环骨架的研究发现
Fan Pu,Axiao Tao,Pengxiang Qiu et al.
Fan Pu et al.
CDK7 has emerged as a highly promising anticancer target, as its dual indispensable roles in cell cycle progression and transcriptional regulation for cancer cell proliferation and survival. Herein, we describe the rational design and ident...
Design and Pictet-Spengler enabled synthesis of carboxamide-substituted imidazo[1,2- a]quinoxalines as dual EGFR and tubulin targeting anticancer agents [0.03%]
设计并通过Pictet-Spengler反应合成带有羧胺取代基的imidazo[1,2-a]quinoxaline类化合物作为靶向EGFR和微管的抗肿瘤药物
Joydeep Chatterjee,Gaurav Joshi,Vibhu Jha et al.
Joydeep Chatterjee et al.
In this study, we report the Pictet-Spengler enabled synthesis of a series of eighteen carboxamide-substituted imidazo[1,2-a]quinoxaline derivatives (JRC-1-JRC-18) targeting epidermal growth factor receptor (EGFR) and tubulin. Compounds JRC...
Systematic identification of bacterial neuraminidase inhibitors from Psoralea corylifolia using ultrafiltration-UPLC-Q-Orbitrap-MS and molecular dynamics [0.03%]
利用超滤-超高性能液相色谱- Orbit 持久性自由基质谱及分子动力学系统地筛选补骨脂中抗细菌神经氨酸酶的成分
Yu Jin Kim,Seol Jang,Youn-Hwan Hwang
Yu Jin Kim
Bacterial neuraminidase (BNA) is a potential target for discovering anti-infective agents. Here, the BNA inhibitory activity of the ethanolic extract of Psoralea corylifolia (EEPC) was investigated using integrated experimental and computat...
Mechanisms of traditional Chinese medicine in enhancing the efficacy and reducing the toxicity of immune checkpoint inhibitors via regulation of the tumor microenvironment and gut microbiota [0.03%]
通过调节肿瘤微环境和肠道菌群增强免疫检查点抑制剂疗效和降低毒性的中医药作用机制
Junying Pan,Liying Yang,Haoyu Wang et al.
Junying Pan et al.
Immune checkpoint inhibitors (ICIs) face challenges of drug resistance and immune-related adverse events (irAEs). Traditional Chinese medicine (TCM)-including single herbs, compounds, and active monomers-enhances ICI efficacy and reduces to...
In vitro screening of compounds for targeting gastric cancer with Y220C p53 mutation: a molecule combining zinc chelation and a Michael acceptor drives CDKN1 and BBC3 expression to restore a p53-dependent cytotoxicity [0.03%]
针对胃癌Y220C p53突变体的体外药物筛选：一种螯合锌离子和迈克尔受体分子通过驱动CDKN1A和BBC3表达来恢复P53依赖性细胞毒性作用
Simon Nannini,Céline Sieffert,Andrew McGown et al.
Simon Nannini et al.
Point mutations in p53 favour tumour aggressivity, particularly in gastric cancer (GC), and offer a target for small molecule-based anticancer treatments. This study focused on the p53-Y220C mutation, which causes p53 misfolding due to ther...
Cadmium inhibits hSMUG1-mediated uracil excision: quantitative analysis and mitigation by Ganoderma lucidum extracts [0.03%]
镉通过抑制hSMUG1介导的尿嘧啶切除作用影响DNA损伤及复制：灵芝提取物可缓解此类危害量化分析
Hui-Lan Chang,Cheng-Hao Fang,Hsing-Lin Chang et al.
Hui-Lan Chang et al.
Cadmium is a pervasive environmental carcinogen known to disrupt multiple DNA repair pathways, yet its direct impact on uracil base excision repair enzyme activity remains unclear. Here, we quantitatively demonstrate that cadmium potently i...
Radioiodinated compound FJR01: a novel P2X7R-targeted SPECT tracer for visualizing glioma-associated microglia/macrophages in a rat glioblastoma model [0.03%]
新型P2X7R靶向SPECT示踪剂FJR01：用于小鼠胶质瘤模型中胶质瘤相关的小胶质细胞/巨噬细胞显像的放射性碘化化合物
Xiyan Rui,Shengxuan Sun,Yuzhou Ding et al.
Xiyan Rui et al.
The P2X7 receptor (P2X7R) is an imaging biomarker of glioblastoma-associated microglia/macrophages (GAMMs), yet no SPECT tracer is currently available for GAMM imaging. Guided by the high-affinity P2X7R scaffold JNJ-64413739 and molecular d...
Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells [0.03%]
独活中的黄酮类化合物通过抑制肌肉和肝脏细胞的PTP1B恢复氧化还原电子流和代谢信号通路
Sang Seop Lee,Jang Hoon Kim,Kyonghwan Bang et al.
Sang Seop Lee et al.
PTP1B is a key negative regulator of insulin and leptin signalling and a promising therapeutic target for metabolic dysfunction, yet no clinically approved inhibitor exists due to selectivity and bioavailability challenges. To identify nove...
Targeting ALDH7A1 with covalent inhibitors reveals new chemical space for prostate cancer therapy [0.03%]
共价抑制剂靶向ALDH7A1揭示了前列腺癌治疗的新化学空间
Raffaella Gallo,Antonio Scarano,Eleonora Gianquinto et al.
Raffaella Gallo et al.
Prostate cancer (PCa) remains a major global health burden. Although androgen deprivation and receptor-targeted therapies initially benefit patients, resistance often leads to metastatic castration-resistant prostate cancer, with limited tr...
Structural optimization of CHI3L1 inhibitors with improved pharmacokinetics and functional activity in 3D glioblastoma models [0.03%]
具有改善的药代动力学和在三维胶质母细胞瘤模型中的功能性活性的CHI3L1抑制剂的结构优化
Baljit Kaur,Hossam Nada,Moustafa T Gabr
Baljit Kaur
Chitinase-3-like protein 1 (CHI3L1) is a key driver of glioblastoma (GBM) progression and an emerging therapeutic target. Building on the CHI3L1 inhibitor 11 g, we optimised the scaffold through medicinal chemistry to assess structure-prope...