The study of a distance learning program using video materials and educational effects - 2D vs. VR randomized controlled trial - The study of a distance learning program using video materials and educational effects

开始日期2023-01-28

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100 项与 Compound 2d(Université de Picardie Jules Verne) 相关的临床结果

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100 项与 Compound 2d(Université de Picardie Jules Verne) 相关的转化医学

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100 项与 Compound 2d(Université de Picardie Jules Verne) 相关的专利（医药）

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项与 Compound 2d(Université de Picardie Jules Verne) 相关的文献（医药）

2024-03-01·European Journal of Medicinal Chemistry

Design, synthesis and antibacterial evaluation of low toxicity amphiphilic-cephalosporin derivatives

Article

作者: Li, Ruirui ; Chen, Shengcong ; Wang, Meng ; Zhang, En ; Qin, Shangshang ; Ampomah-Wireko, Maxwell ; Nininahazwe, Lauraine ; Qu, Ye ; Gao, Chen

Global public health is facing a serious problem as a result of the rise in antibiotic resistance and the decline in the discovery of new antibiotics. In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 μg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a longer post-antibiotic effect (PAE) than vancomycin. Mechanism studies indicated that compound 2d lacks membrane-damaging properties and can target penicillin-binding proteins to disrupt bacterial cell wall structure, inhibit the metabolic activity and induce the accumulation of reactive oxygen species (ROS) in bacteria. Compound 2d showed minimal drug resistance and was nontoxic to HUVEC and HBZY-1 cells with CC₅₀ > 128 μg/mL. These findings suggest that 2d is a promising drug candidate for treating bacterial infections.

2020-02-01·European Journal of Medicinal Chemistry

Development of selective mono or dual PROTAC degrader probe of CDK isoforms

Article

作者: Zhou, Fei ; Xie, Yongmei ; Zhou, Peiting ; Luo, Xiaojiao ; Cheng, Jijun ; Du, Wu ; Chen, Luyu ; Yu, Jiang ; Chen, Yuanwei ; Cao, Chaoguo ; Zhao, Lifeng

Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation. In discovering inhibitors of these CDKs, toxicity associated with off-target effect on other CDK homologs often posts as a clinical issue and hinders their further therapeutic development. To improve efficacy and reduce toxicity, here, using the Proteolysis Targeted Chimeras (PROTACs) approach, we design and further optimize small molecule degraders targeting multiple CDKs. We showed that heterobifunctional compound A9 selectively degraded CDK2. We also identified a dual-degrader, compound F3, which potently induced degradation of both CDK2 (DC₅₀: 62 nM) and CDK9 (DC₅₀: 33 nM). In human prostate cancer PC-3 cells, compound F3 potently inhibits cell proliferation by effectively blocking the cell cycle in S and G2/M phases. Our preliminary data suggests that PROTAC-oriented CDK2/9 degradation is potentially an effective therapeutic approach.

2020-01-01·Bioorganic Chemistry2区 · 化学

Design, synthesis and anti-HBV activity of NVR3-778 derivatives

2区 · 化学

Article

作者: Lv, Kai ; Li, Yuhuan ; Wu, Meng ; Wu, Shuo ; Li, Wenyan ; Gao, Qiang ; Zhou, Jinming ; Liu, Mingliang ; Geng, Yunhe

NVR3-778, one of the most advanced capsid assembly modulators (CAMs), is currently in phase II clinical trial for the treatment of HBV infection. In this study, we reported the first structure optimization of NVR3-778. Compound 2d was found to exhibit more potent anti-HBV activity (IC₅₀: 0.25 µM), lower cytotoxicity (CC₅₀: 10.68 µM) and higher selectivity index (SI: 40.72) than NVR3-778 (IC₅₀: 0.33 µM; CC₅₀: 5.14 µM; SI: 18.36) in vitro, and also display similar inhibitory effect on the assembly of HBV capsids as NVR3-778. Molecular docking further suggested that compound 2d might form a stronger interaction with core protein. Moreover, compound 2d also showed acceptable pharmacokinetic profiles. Currently compound 2d was selected as a new lead for further modifications, and studies to determine the in vivo anti-HBV studies of 2d will begin soon.

100 项与 Compound 2d(Université de Picardie Jules Verne) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
伯克霍尔德氏菌属感染	临床前	法国	Université De Picardie Jules Verne	2022-11-13
假单胞菌感染	临床前	法国	Université De Picardie Jules Verne	2022-11-13