相关实验视频

Updated: May 29, 2025

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

通过虚拟查和SAR驱动合成,通过计算机辅助发现新型AMPK激活剂

Kyung-Hwa Jeon¹, Jae-Ho Shin², Hyun-Ji Jo³

¹College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Republic of Korea; Gradutate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Korea.

European journal of medicinal chemistry

|February 4, 2025

概括

研究人员开发了一种新的AMP激活蛋白激酶 (AMPK) 小分子激活剂. 通过虚拟查和合成识别的这种化合物显示出治疗糖尿病和阿尔茨海默病等代谢障碍的潜力.

科学领域:

生物化学生物化学
药用化学医学化学
药理学药理学是指药理学的学科.

背景情况:

AMP激活蛋白激酶 (AMPK) 是细胞能量代谢的关键调节剂.
AMPK的失调与包括糖尿病和阿尔茨海默病 (AD) 在内的慢性疾病有关.
向AMPK为代谢障碍提供了潜在的治疗策略.

研究的目的:

发现和开发新的小分子,直接激活AMPK.
为了确定AMPK激活的新药.
探索对代谢和神经退行性疾病的潜在治疗剂.

主要方法:

一个大型化学库的基于结构的虚拟选.
在基分子对接和代优化.
在体外和细胞测试以评估AMPK激活.
合成和评估新型的石墨烯衍生物.

主要成果:

通过虚拟选,通过虚拟选识别了一个基于染色体的命中化合物 (B1).
作为AMPK激活的卓越支架,发现了石墨烯衍生物.
化合物6在体,体外和细胞模型中显示出强大的AMPK激活.
化合物6与关键的AMPK残留物表现出有效的相互作用.

结论:

基衍生物对AMPK激活剂来说是一个有前途的新支架.
化合物6是进一步开发AMPK相关疾病治疗剂的有力候选者.
直接AMPK激活有可能调节代谢障碍中的致病机制.

更多相关视频

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Published on: January 27, 2014

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors

Published on: August 17, 2019

相关概念视频

cAMP-dependent Protein Kinase Pathways

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...