描述可提取和可化化学空间,以支持中的毒理危害评估
Candice Johnson1, Arianna Bassan2, Doug Kiehl3
1Instem, 1393 Dublin Road, Columbus, OH; candice.johnson@instem.com.
PDA journal of pharmaceutical science and technology
|June 28, 2024
概括
分析了783个可提取物和可浸物 (E&L) 的综合数据集,揭示了142个化学类. 许多E&L化学物质显示出潜在的致变性或皮肤敏感性,这些风险之间存在明显的重叠.
科学领域:
- 制药分析 制药分析
- 化学安全评估 化学安全评估
- 毒理学 毒理学 毒理学
背景情况:
- 提取和漏 (E&L) 是制药产品开发中的关键安全考虑因素.
- 来自可提取和可漏安全信息交换 (ELSIE) 联盟和产品质量研究院 (PQRI) 的现有数据集提供了有价值的E&L信息.
- 需要一个全面的,具有代表性的数据集来理解E&L概况和相关风险.
研究的目的:
- 通过结合ELSIE和PQRI数据,开发一个统一的,代表性的可提取物和可浸出物 (E&L) 数据集.
- 分析化学物质的多样性,并确定E&L环境中的常见类别.
- 评估在联合E&L数据集中的潜在危险化学结构,特别是变异原体和强烈皮肤敏感剂的流行程度.
主要方法:
- 结合了ELSIE和PQRI发布的E&L数据集,共计783种化学品.
- 采用基于化学结构的聚类来将化学物质分类为不同的类别.
- 使用 *in silico* 毒理学工具来预测潜在的致病性和皮肤敏感性.
主要成果:
- 从组合数据集中确定了142个不同的化学品类,其中105个类包含来自ELSIE和PQRI的化学品.
- 大约9%的E&L化学物质被标记为潜在的变异原体,3%被标记为强烈的皮肤敏感剂.
- 观察到一个显著的重叠,80%的强效皮肤敏感剂也被预测为变异原体. 基化物和异基酸盐被确定为具有潜在危害的独特PQRI类.
结论:
- 结合的ELSIE-PQRI数据集为E&L评估提供了一个强大的资源.
- 很大一部分E&L化学物质具有对变异性和/或强烈皮肤敏感性的结构性警报.
- 突变性和敏感性警报的同时出现强调了需要对E&L化合物的仔细风险评估.
更多相关视频
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
2.7K
11:38High Content Screening Analysis to Evaluate the Toxicological Effects of Harmful and Potentially Harmful Constituents HPHC
Published on: May 10, 2016
12.2K
相关概念视频
Extraction: Advanced Methods
446
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...
446
Types of Toxins
1.7K
Humans continually engage with an environment rich in potentially harmful chemicals. These are introduced to our bodies through inhalation, ingestion, or skin contact. These chemicals exist in various forms, such as air and environmental pollutants, agricultural chemicals, organic solvents, and heavy metals.
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
Air pollutants, primarily gases, pose significant threats to respiratory health, leading to conditions like hypoxia, lung cancer, and in extreme cases, death.
Environmental pollutants like...
1.7K
Mutagenicity and Carcinogenicity
1.2K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.2K
Drug Discovery: Overview
7.8K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.8K
Structure-Activity Relationships and Drug Design
697
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
697
