Hyper ADME/T

Hyper ADME/T is a feature that predicts the PK/PD properties and toxicity of registered molecules using AI.

In medicinal chemistry, it is essential to evaluate ADME/T suitability—Absorption (A), Distribution (D), Metabolism (M), Excretion (E), and Toxicity (T)—based on the physicochemical properties of a compound. Hyper ADME/T leverages AI technology to predict these key indicators and provides three different calculation methods.

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1. How to run Hyper ADME/T

1.1. Calculate from Bench

You can run Hyper ADME/T by clicking the Run button in the Hyper ADME/T field within Bench.

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2. ADME/T Prediction Result Description

2.1. Physicochemical properties

• LogD at pH7.4: Predicted log value of the octanol–water distribution coefficient at physiological pH 7.4, including both ionized and unionized species (dimensionless, pH-dependent).

• Solubility: log S (in unit log [mol/L]) at the neutral pH is predicted to indicate the solubility according to the following criteria.

  • Insoluble: logS<−6logS < -6logS<−6

  • Moderate: −6≤logS≤−4-6 \le logS \le -4−6≤logS≤−4

  • Soluble: −4≤logS-4 \le log S−4≤logS

2.2. Medicinal chemistry

• Druglikeness: Druglikeness here is predicted based on a density estimation of known drugs. [Chem. Sci. 13: 554 (2022)]. The closer the value to 100, the more likely the compound is to be a drug. The average values for typical databases are as follows:

  • FDA-approved drugs: 74.5

  • ChEMBL molecules: 60.5

• Synthesis complexity: The value predicts the number of steps needed to synthesize the compound using commercially available building blocks and well-established chemical reactions [J. Chem. Inf. Model. (2023)].

• CNS MPO: A multiparameter score (0–6) for CNS drug design; higher scores indicate greater favorability for CNS drug design. In HyperLab, the score is calculated according to the CNS MPO scoring system published in 2017, based on five physicochemical properties: LogP, TPSA, Molecular weight, Most basic pKa, and Number of hydrogen bond donors (with double weighting).

  [J. Med. Chem. 2017, 60, 5943−5954]

2.2. ADME/T

• Metabolic stability: “Unstable” means that, when tested in a human/mouse liver microsome assay, the compound is likely to degrade by more than 50% within 30 miniutes at a concentration of 2μM.

• PAMPA: “High” means the compound’s permeability is likely over 7x10^-6 cm/s.

• P-gp inhibitor: “Yes” means the compound’s RF* from the multidrug resistance reversal (MDRR) assay is likely over 5; “No” means the RF is likely under 4. (*Reversal fold = [ED50 w/o adriamycin] / [ED50 w/ adriamycin])

• BBB penetration: “High” means the compound’s log ([concentration in brain / [concentration in blood]) is likely over -1.

• CYP inhibitor: “Yes” means the compound’s IC50 is likely under 10 μM.

  • CYP1A2 inhibitor

  • CYP2C19 inhibitor

  • CYP2C9 inhibitor

  • CYP2D6 inhibitor

  • CYP3A4 inhibitor

• CYP substrate: “Yes” means the compound is likely a substrate of the CYP enzyme.

  • CYP1A2 substrate

  • CYP2C19 substrate

  • CYP2C9 substrate

  • CYP2D6 substrate

  • CYP3A4 substrate

• hERG inhibitor: “Yes” means the compound’s IC50 is likely under 10 μM