新的机器学习模型用于预测有机阴离子载体OCT1,OCT2和OCT3的摄取量
Giovanni Bocci1, Neann Mathai2, Benjamin Suutari2
1Recursion, The HKX Building, 3 Pancras Square, London N1C 4AG, U.K.
ACS omega
|October 6, 2025
概括
新的机器学习模型预测有机离子载体 (OCT) 药物吸收. 这些具有成本效益的in silico工具通过预测药物动力学负债来帮助早期药物发现,改善药物开发.
科学领域:
- 药理学 药理学是指药理学的学科.
- 计算化学的计算化学
- 生物化学 生化学
背景情况:
- 有机阴离子载体 (OCT) 对药物药理动力学 (PK) 具有至关重要的作用,影响吸收和排泄.
- 目前用于评估小分子的OCT调制的实验方法昂贵且耗时.
- 准确的in silico模型是必要的,以便在药物候选物中早期预测PK负债.
研究的目的:
- 开发和验证机器学习 (ML) 模型,用于预测有机阴离子载体1,2和3 (OCT1,OCT2,OCT3) 的吸收.
- 提供一个具有成本效益的计算工具,用于预测与海外国家和地区的药物相互作用.
- 在药物发现过程中帮助早期识别潜在的PK负债.
主要方法:
- 利用先进的决策树整体算法进行模型构建.
- 使用VolSurf分子描述器作为机器学习模型的特征.
- 经过训练和验证的模型,用于最大的可用策划数据集,用于OCT介导的吸收.
主要成果:
- 开发了具有显著预测能力的ML模型,用于OCT1,OCT2和OCT3的吸收.
- 在多个外部验证轮中达到超过0.45的马修斯相关系数 (MCC) 值.
- 证明了开发的in silico模型的稳定性和准确性.
结论:
- 开发的ML模型为预测OCT介导药物吸收提供了实验性分析的成本效益替代方案.
- 这些模型可以通过早期预测PK负债来显著帮助药物发现.
- 这些研究结果为了解和减轻在药物开发中与OCT相关的挑战提供了有价值的工具.
相关概念视频
The Significance of Membrane Transport
41.0K
The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
41.0K
ABC Transporters: Exporter
6.3K
ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
6.3K
Carrier-Mediated Transport
1.2K
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
1.2K
Primary Active Transport
13.6K
In contrast to passive transport, active transport involves a substance being moved through membranes in a direction against its concentration or electrochemical gradient. There are two types of active transport: primary active transport and secondary active transport. Primary active transport utilizes chemical energy from ATP to drive protein pumps embedded in the cell membrane. With energy from ATP, the pumps transport ions against their electrochemical gradients—a direction they would...
13.6K
Membrane Transporters
17.7K
Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
17.7K
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
277
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
277


