相关实验视频

Updated: Sep 15, 2025

Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays

Direct Measurement of KDM1A Target Engagement Using Chemoprobe-based Immunoassays

Published on: June 13, 2019

探索基于氨酸的小分子作为KDM4抑制的金属合剂

Angus J Saxton¹, Jayden Sterling², Michael P Hamilton¹

¹Chemistry, School of Environmental and Life Sciences, The University of Newcastle Callaghan NSW 2308 Australia jenniferb@uow.edu.au.

RSC medicinal chemistry

|July 14, 2025

概括

研究人员合成并选了81种向癌症治疗的组合物,这些组合物是向基氨酸脱甲基酶 (KDMs). 化合物72显示出最显著的KDM4A抑制,具有潜在的表观遗传癌症治疗.

科学领域:

药用化学医学化学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
癌症治疗方法癌症治疗方法

背景情况:

氨酸衍生物是开发铁依赖的二氧化酶的抑制剂的关键.
基因组 lysine 脱甲基酶 (KDMs) 是表观遗传癌症治疗中的关键标.
在癌症中KDM4A的作用需要开发向抑制剂.

研究的目的:

为了合成和选KDM4A抑制活性的新型化合物.
探索基于氨酸的KDM4A抑制剂的结构-活性关系.
为了确定潜在的癌症治疗的强大的KDM4A抑制剂.

主要方法:

合成了四个化合物库 (共81个化合物).
使用针对KDM4A.优化的AlphaScreen试验对化合物的查.
分子建模 (MOE) 用于预测结合姿势和相互作用.

主要成果:

图书馆1 (3-((2-基化) 甲基酸) 显示轻微抑制;化合物16,17,24,28,38是最活跃的.
图书馆2 (3-((2-hydrazono) 甲基) 酸) 一般缺乏活性,除了化合物46.
图书馆4 (甲基衍生物) 显示抑制降低,但化合物70和72显示改善活性,其中72是最强的 (在20μM下<40%的残留活性).

结论:

该研究确定了基于氨酸支架的新型KDM4A抑制剂.
结构性修改影响了抑制活性,特定化合物显示出有前途.
分子建模表明,碳酸或氨酸部分的金属化是抑制的关键,支持KDM4A作为一个可行的治疗标.

更多相关视频

Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs

Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs

Published on: January 17, 2020

Preparation of SNS CobaltII Pincer Model Complexes of Liver Alcohol Dehydrogenase

Preparation of SNS CobaltII Pincer Model Complexes of Liver Alcohol Dehydrogenase

Published on: March 19, 2020

相关概念视频

Metal-Ligand Bonds

Metal-Ligand Bonds

The hemoglobin in the blood, the chlorophyll in green plants, vitamin B-12, and the catalyst used in the manufacture of polyethylene all contain coordination compounds. Ions of the metals, especially the transition metals, are likely to form complexes.
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...

Complexation Equilibria: The Chelate Effect

Complexation Equilibria: The Chelate Effect

In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...

EDTA: Chemistry and Properties

EDTA: Chemistry and Properties

Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...

Masking and Demasking Agents

Masking and Demasking Agents

EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on...

Formation of Complex Ions

Formation of Complex Ions

A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...

Extraction: Advanced Methods

Extraction: Advanced Methods

Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...