Hyper ADME/T

Running Hyper ADME/T

The process for performing Hyper ADME/T on the registered molecules is as follows.

In the list of molecules in the Molecule List, you will see a blue icon labeled Result in the Hyper ADME/T column.

By clicking on the Result, you can see the Molecule Information page.

You can see the ADME/T column in Molecule Information page.

You can see the Purchase link when you use Hyper Screening.

When you enter the molecule details page, you will see that the AI prediction value is entered into the Binding Score row and the icon in the 3D View section of the 3D structure the row is activated. You can also check the ADME/T prediction results.

Field/Property Explanation

• Creation date: This is the date the molecule war registered

• Created by: This is the user who first registered each molecule

• Book mark: Important molecules can be marked using the bookmark feature. This also can be used as a group of molecules (custom grouping).

• Hyper Screening: This is the library tag used during Hyper Screening.

• Lipinski rule: So-called Rule of 5 (RO5). RO5 criteria: Molecular weight equal to or less than 500 Da, logP equal to or less than 5, hydrogen bond acceptors equal to or less than 10, and hydrogen bond donors equal to or less than 5.

• Veber's (GSK rule) : Molecules that satisfy this rule may have a favorable ADMET profile. Criteria: Total polar surface area (TPSA) equal to or less than 140 $Å^2$, rotatable bonds equal to or less than 10.

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

  • Insoluble: $logS < -6$

  • Moderate: $-6 \le logS \le -4$

  • Soluble: $-4 \le log S$

• Metabolic stability: 'Unstable' means that, when tested in a human liver microsomes assay, the compound is likely to degrade by more than 50 % within 30 minutes at a concentration of 1 µM.

• PAMPA: 'High' means the compound's permeability is likely over $7 \times 10^{-6} cm/s$

• BBB: 'Permeable' means the compound's $log {[concentration\ in\ brain] \over [concentration\ in\ blood]}$is likely over -1. This means that the compound in the brain concentration should be at least 10 %.

• Druglikeness: Drug-likeness here is predicted based on a density estimation of known drugs. 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

  • GDB-17 molecules: 40.5 (currently database not accessible)

• 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. 2024, 64, 7, 2432–2444]

• CYP1A2 inhibitor: 'Yes' means the compound's IC50 against CYP1A2 is likely under 10 µM.

• CYP1A2 substrate: 'Yes' means the compound is likely a substrate of the CYP1A2 enzyme.

• CYP2C9 inhibitor: 'Yes' means the compound's IC50 against CYP2C9 is likely under 10 µM.

• CYP2C9 substrate: 'Yes' means the compound is likely a substrate of the CYP2C9 enzyme.

• CYP2C19 inhibitor: 'Yes' means the compound's IC50 against CYP2C19 is likely under 10 µM.

• CYP2C19 substrate: 'Yes' means the compound is likely a substrate of the CYP2C19 enzyme.

• CYP2D6 inhibitor: 'Yes' means the compound's IC50 against CYP2D6 is likely under 10 µM.

• CYP2D6 substrate: 'Yes' means the compound is likely a substrate of the CYP2D6 enzyme.

• CYP3A4 inhibitor: 'Yes' means the compound's IC50 against CYP3A4 is likely under 10 µM.

• CYP3A4 substrate: 'Yes' means the compound is likely a substrate of the CYP3A4 enzyme.

• hERG inhibitor: 'Yes' means the compound's IC50 is likely under 10 µM.

• P-gp inhibitor: 'Yes' means the compound's Reversal Fold (RF) ratio is more than 5. 'No' means the RF ratio is likely under 4.

  • P-glycoprotein (P-gp) causes a multidrug resistance (MDR) phenotype in tumor cells. The RF ratio is used in multidrug resistance reversal (MDRR) assay.

  • RF = $ED50\ w/o\ adriamycin \over ED50\ w\ adriamycin$

• Chemical formula: Show the composition of atoms.

• Heavy atoms: This is the number of atoms in each molecule, excluding hydrogen.

• Rotatable bonds: This is the number of rotatable bonds.

• Hydrogen bond donors: This is the number of hydrogen bond donors in the molecule.

• Hydrogen bond acceptors: This is the number of hydrogen bond acceptors in the molecule.

• Molar refractivity: This is the total polarizability of one mole of the molecule.

• FSP$^3$: The number of SP3 hybridized carbons/total carbon count. Generally, a ratio of 0.42 or higher is appropriate.

• Experiment, IC50: Experimental IC50

• Experiment, EC50: Experimental EC50

• Tag: Custom tag to distinguish your molecule group

• Protein Target - Binding Score: Hyper Lab Binding Score (Protein Target: activated protein in your bench/project bench)