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...
Design, synthesis, and biological evaluation of tyrcinnamine derivatives as bactericides [0.03%]
酪氨链霉素衍生物的 дизайн, 合成和 生物 评价作为细菌icide
Lijie Zheng,Baoyue Wei,Ji Pang et al.
Lijie Zheng et al.
Structural modification of bioactive natural products plays a vital role in the development of new drugs. Herein, we report the design and synthesis of twelve new tyrcinnamin derivatives (6a-8a, 6b-7b, 6c-8c, 10, and 13-15) using tyrcinnami...
2 H-pyrazolo[3,4- d]pyrimidin-4-amine derivatives as novel selective fibroblast growth factor receptor 2 (FGFR2) inhibitors [0.03%]
两种H-吡唑并[3,4-d]嘧啶-4-胺衍生物作为新型选择性成纤维细胞生长因子受体2（FGFR2）抑制剂的研究
Pinglian Wu,Zhaodi Tian,Weizhong Shen et al.
Pinglian Wu et al.
Although FGFR2 is a well-validated oncogenic target, no selective FGFR2 inhibitors have been approved for clinical use. In this study, we report the discovery of 2H-pyrazolo[3,4-d]pyrimidin-4-amine derivative as novel, irreversible FGFR2 in...
PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators [0.03%]
癌细胞治疗中的靶向蛋白降解：GPX4、PARP及表观遗传调控因子 PROTACs 的研究进展
Sunny Periyasamy,Thyla Jarrett,Joe Truong et al.
Sunny Periyasamy et al.
The degradation of overexpressed proteins has emerged as a promising strategy for halting disease progression, particularly in cancer. Traditional small-molecule drugs often face limitations in the elimination of pathogenic proteins, leadin...