跳转至

ADMET 用户指南

1. 算法简介

ADMET 评价是对药物的吸收、分布、代谢、排泄和毒性性质的全面研究；药物早期的 ADMET 性质评价可显著地提高药物研发的成功率。

本模块提供一系列基于信息传递神经网络和注意力机制的 ADMET 性质预测模型，并通过多视角（Multi-view）建模优化；这些模型可以用于快速准确的计算候选药物分子的理化性质、毒性信息和药代动力学相关性质等，同时给出模型预测的依据、提高模型的可解释性和可信度。

2. 使用流程

2.1 上传分子

平台提供了两种数据输入方式：输入SMILES表达式和上传包含分子式的文件。

  • 输入SMILES表达式

    复选框选中“输入SMILES”，通过文本框输入一个或多个SMILES表达式（多个SMILES使用英文逗号分隔）；

    或点击文本框末端的“DRAW”图标，在弹出的编辑器中画出分子（仅1个），点击“确认”后转换成SMILES显示在文本框中。

    img

    img

  • 上传包含分子式的文件

    复选框选中“上传包含分子式的文件”，点击“文件上传”按钮上传文件。

    img

    上传的文件需要满足以下条件：

    • 当前支持的文件格式：sdf/csv/mol2/xls/xlsx/txt
    • 文件中分子数量不超过100
    • 文件大小不超过10MB
    • 文件中SMILES表达式的列名为“smiles”或“SMILES”，下图提供了示例：

    img

2.2 提交任务

完成数据输入后，点击“提交”按钮即可提交任务。任务会在10min时间内完成并显示结果。

为了合理的分配有限的资源，我们对用户的任务额度进行了一定的限制，鼠标悬停在“提交”按钮上可以看到限制情况与使用情况。(任务数=预测分子数量)

img

3. 查看结果

3.1 查看结果详情

任务完成后页面立刻显示分子的预测结果。

  • 输入框输入的分子预测结果包括分子结构图、雷达图、分子属性：

    1）分子结构图和雷达图：

    2）分子属性

  • 文件上传的分子预测结果通过表格来展示：

    img

3.2 查询历史记录

点击页面上方“历史记录”标签，可以查看最近20个任务结果。

img

4. ADMET属性说明

ADMET Property Output Illustration
Thermodynamic Solubility (abbr. ts, tsc1, tsc10, tsc100) a thermodynamic water solubility value (logrithm of mol/L) per molecule. The value is a direct measure of the solubility of the molecule. We provided four thermodynamic solubility model, where ts is a regression model, tsc1 is a classification model which cutoff is 1uM/L. Likewise, tsc10 and tsc100 use 10 uM/L and 100 uM/L as cutoff.
Caco-2 permeability (apical to basolateral) A CACO-2 permeability value (Papp，10^-6 cm/s). The value can be used to evaluate the human intestinal permeability.
Blood-Brain Barrier Permeability (BBBP) probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to pass through the blood brain barrier if the value is high.
Human intestinal absorption (HIA) probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to be absorbed if the value is close to 1.
Plasma Protein Binding (PPB) (human) The percentage of chemicals bound to plasma protein (between 0 and 1) per molecule.
pKa Strongest acidic pKa and strongest basic pKa per molecule. If no acidic functional group or basic functional group is found in the molecule, that line will be n/a.
Tox21 probability Qualitative toxicity measurements on 12 biological targets, including nuclear receptors and stress response pathways. Output as 12 probability value (between 0 and 1) per molecule. Each subtitle displayed on the result page implies the specific tox endpoint.
hERG inhibition probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to be hERG inhibitor.
hERG inhibition probability (c10) A probability value of molecule’s IC50 value below that threshold (10 uM). If the value is close to 1, the IC50 is more likely to be lower than the threshold. Which means it is an inhibitor.
hERG inhibition probability (c50) A probability value of molecule’s IC50 value below that threshold (50 uM). If the value is close to 1, the IC50 is more likely to be lower than the threshold. Which means it is an inhibitor.
P-gp substrate probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to be a p-glycoprotein substrate if the value is close to 1.
P-gp inhibition probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to be a p-glycoprotein inhibitor if the value is close to 1.
logD (pH7.4) Distribution coefficients at pH 7.4 (logD7.4).
HLM-CL𝚒𝚗𝗍 (μL/min/mg) An estimate value of in vitro human liver microsome metabolic stability (base 10 logrithm of mL/min/g).
MLM-CL𝚒𝚗𝗍 (μL/min/mg) An estimate value of in vitro mouse liver microsome metabolic stability (base 10 logrithm of mL/min/g).
RLM-CL𝚒𝚗𝗍 (μL/min/mg) An estimate value of in vitro rat liver microsome metabolic stability (base 10 logrithm of mL/min/g).
CYP inhibition probability A probability value(between 0 and 1) of a molecule to be the inhibitor of CYP 1A2, 2C19, 2C9, 2D6, 3A4.
Oral Bioavailability (human) A bioavailability value (between 0 and 1) per molecule. The molecule has high oral bioavailability if the value is close to 1.
Ames Toxicity probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to induce ames toxicity if the value is close to 1.
Hepatic Toxicity probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to induce hepatotoxicity if the value is close to 1.
Hek293 Toxicity probability A probability value (between 0 and 1) per molecule. The molecule is highly possible to induce hek293 toxicity if the value is close to 1.
Kinetic Solubility A kinetic solubility value (base 10 logrithm of mol/L) per molecule. The value is measured at pH 7.4 and 25℃ in PBS.
PAMPA A PAMPA permeability value (Papp，10^-6 cm/s).
MDCK In vitro passive membrane permeability across multidrug resistance Madin-Darby canine kidney (MDCK) cell monolayers with unit of log(10^-6 cm/s)，the direction was apical to basal.
DILI A probability value (between 0 and 1) ). A molecule is highly possible to induce liver injury if the vale is close to 1.
Carcinogenicity A probability value (between 0 and 1) ). A molecule is highly possible to be carcinogenicity if the vale is close to 1.
Tubulin inhibition A probability value (between 0 and 1) ). A molecule is highly possible to inhibit tubulin if the vale is close to 1.
Mutageniciy A probability value (between 0 and 1) ). A molecule is highly possible to be mutagenicity if the vale is close to 1.
CYP induction A probability value (between 0 and 1) ). A molecule is highly possible to induce cytochrome P450 by evaluating mRNA levels and/or catalytic activity if the vale is close to 1.
Genotoxicity A probability value (between 0 and 1) ). A molecule is highly possible to be genotoxic if the vale is close to 1.
Reproductive toxicity A probability value (between 0 and 1) ). A molecule is highly possible to have a reproductive toxicity if the vale is close to 1.
Eye irritation A probability value (between 0 and 1) ). A molecule is highly possible to cause dryness, itching, pain, or grittiness of the eye if the vale is close to 1.
Eye corrosion A probability value (between 0 and 1) ). A molecule is highly possible to cause tissue damage in the eye, or serious physical decay of the vision if the vale is close to 1.
Phototoxicity A probability value (between 0 and 1) ). A molecule is highly possible to make the skin or eyes become very sensitive to sunlight if the value is close to 1.
phospholipidosis A probability value (between 0 and 1) ). A molecule is highly possible to induce intracellular accumulation of phospholipids in tissues if the value is close to 1.
Human clearance A human clearance value (log10 of ml/min/kg). Human clearance is a measure of excretion ability of a molecule by a human body.
Blood brain ratio A value (log10) measure the ratio of brain concentration to blood concentration of a molecule.
LD50 A median lethal dose (log10 of mg/kg). LD50 value of a molecule is the dose required to kill half the members of the tested population.