药物发现和开发中的免疫毒性概述
Rahul M Nandre1, Pramod S Terse1
1Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, NIH, Rockville, MD, United States.
Toxicology letters
|November 27, 2024
概括
评估药物免疫毒性对于患者安全和监管合规性至关重要. 本综述强调了各种体外和体内方法对于评估药物在发育过程中对免疫系统的影响的重要性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 毒理学 毒理学 毒理学
背景情况:
- 免疫系统经常受到药物毒性 (免疫毒性) 和疗效 (免疫疗法) 的影响.
- 药物诱导的免疫毒性对人类健康构成重大风险,促使监管机构对其进行审查.
- 目前的评估涉及不同的体外和体外方法.
研究的目的:
- 强调免疫毒性评估在药物发现和开发中的关键作用.
- 倡导探索基于人类细胞的in silico和in vitro测试,以进行高效的查.
- 概述非临床体内免疫毒性研究的分层方法.
主要方法:
- 审查当前的体外和体内免疫毒性评估策略.
- 讨论分层的体内评估 (1-3级),包括血液学,免疫类型和宿主耐药性.
- 考虑在选中使用in silico和基于人类细胞的试验.
主要成果:
- 免疫毒性评估对于识别药物不良影响至关重要.
- 分层体内研究为选择临床试验终点和标签提供了数据.
- 在 silico 和 in vitro 方法提供了具有成本效益和道德性的查替代方案.
结论:
- 在整个药物开发过程中,全面的免疫毒性评估至关重要.
- 结合in silico,in vitro和分层in vivo方法,可确保安全性评估的可靠性.
- 准确报告免疫毒性数据有助于医疗保健专业人员安全处方和患者管理.
相关概念视频
01:28Preclinical Development: Overview
4.2K
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
4.2K
01:26Drug Discovery: Overview
7.5K
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...
7.5K
01:27Effects of Chemicals: Overview
1.2K
Drugs, encompassing various chemical compounds from natural sources, lab synthesis, or genetic engineering, elicit different biological responses in living organisms. Some of these responses are desirable or therapeutic, while others are undesirable. The primary goal of administering a drug is to achieve a therapeutic effect, that is, to address a specific disease or health condition. Any concurrent effects outside of this therapeutic outcome are considered undesirable. These undesirable...
1.2K
01:25Mutagenicity 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
01:26Toxic Reactions: Overview
947
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
947
01:25Drug Regulation
1.3K
Drug regulation encompasses the management of drug usage by evaluating its safety and efficacy through assessments conducted by regulatory authorities. Regrettably, the history of drug regulation is marred by several catastrophic events. One such incident is the Elixir Sulfanilamide tragedy, in which the toxic compound diethyl glycol was included in a sweet-tasting medication, leading to numerous fatalities. This event prompted the enactment of the Food, Drug, and Cosmetic Act in 1938. Under...
1.3K