Fields

1. Default Fields

HyperLab shows Derivative, Design type, Name, Structure, Hyper Binding, Hyper ADME/T, Hyper Design, Molecular weight, LogP, and TPSA fields by default.

2. Field Editing and Activation

2.1. All Fields

1. Click the Field button in the top-right corner to open the field tab.

2. In All tab, you can view all fields provided by HyperLab as well as custom fields you have created.

2.2. Activated Fields

1. In the Activated tab, you can edit the display status of the fields currently shown in the Bench table.

2. Click the eye icon on each field to toggle its visibility in the Bench.

3. Drag and drop each field to change the display order in the Bench.

*For Shared Benches, project members cannot change the visibility or order of fields.

2.3. Custom Fields

In addition to the default fields provided by HyperLab, users can create custom fields and directly input data.

1. In the Field Management screen, click Create a new field to open the field creation window.

2. Enter a field name, select a field type, and add it to the Bench.

3. Supported data types for custom fields are limited to Text, Number, and Tag formats.

3. Field criteria

3.1. Compound information

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

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

• Derivative: This is the number of derivatives of the molecule.

• Name: The names of the molecules.

• Structure: This is the 2D structure of the molecules.

3.2. Hyper Screening X

• Hyper Screening X model: This is the tag of the model selected for molecule generation through Hyper Screening X.

• Hyper Screening X route: You can check the synthesis pathway and BB information of the molecules generated by Hyper Screening X.

3.3. HyperLab features

• Hyper ADME/T: Hyper ADME/T can be performed in this field. The calculation results can be viewed on the detailed page of each molecule or by adding the relevant field to the current table.

• Hyper Binding: Hyper Binding can be performed on the currently activated protein. (The activated protein can be modified in the Protein Structure) After the calculation is complete, the result will be displayed. The smaller this value, the stronger the binding with the protein, which indicates high activity.

• Hyper Design: This indicates whether hyper design has been performed on the molecule.

3.4. Hyper Design results

• Design structure: This is the activated protein structure utilized in the Hyper Design of this molecule. The structure is provided in tag format.

• Design type: Show molecules generated by Hyper Design.

• R group definition: This is the R group tag, which displays the R group defined when using the Hyper Design. They are selected through the R group definition.

3.5. Hyper Screening

• Enamine link: This is the Enamine link to purchase the compounds added through Hyper Screening.

• Molport link: This is the Molport link to purchase the compounds added through Hyper Screening.

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

• Vendor ID: This is the vendor's catalog ID for compounds added through the Hyper Screening process.

• Vendor name: This is the vendor name for compounds added through Hyper Screening, displayed as a tag.

3.6. Physicochemical properties

• Chemical formula: Show the composition of atoms.

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

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

• 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.

• LogD₇․₄: Predicted log value of the octanol–water distribution coefficient at physiological pH 7.4, including both ionized and unionized species (dimensionless, pH-dependent).

• LogP: A predicted value for the logarithm of octanol–water partition coefficient (dimenionless).

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

• Molecular weight: This is the molecular weight of each molecule.

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

• 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: $-4 \le log S$

• TPSA: It is defined as the sum of the molecular polar surface areas. If this value exceeds 140 (Ų), there is a high probability that it will not permeate the cell membrane.

3.7. Medicinal chemistry

• 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]

• Druglikeness: Drug-likeness 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

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

• 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.

• 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]

• 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.

3.8. Hyper ADME/T results

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

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

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

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

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

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

3.9. CYP inhibition

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

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

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

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

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

3.10. CYP substrate

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

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

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

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

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

3.11. Binding scores

Protein Target - Binding Score: Hyper Binding results for each protein structure. For calculation, please activate the protein structure and then execute the calculation in the Hyper Binding field.

3.12. Experimental value

• Experiment, IC50: Experimental IC50

• Experiment, EC50: Experimental EC50

3.13. Others

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

• Tag: Custom tag to distinguish your molecule group