This StarDrop script estimates free fraction (fᵤ) in microsomes, hepatocytes, and plasma from experimental data in other media, experimental logD or, in their absence, predicted logD. Practically, it lets you correct assay readouts and convert intrinsic clearance to unbound values (Clint/fᵤ), enabling cleaner cross-assay comparisons and faster decisions.
It does this based on linear relationships between experimentally determined partition coefficients in different media, and, where data from multiple media are available, prioritises the input data expected to give the most accurate results.
Full details of the derivation and application of these models are provided in the presentation below, given by Mark Gardner of AMG.
We would like to thank Medicines for Malaria Ventures (MMV), Mark Gardner, and Jérémy Besnard, who derived the underlying models from MMV’s proprietary data. The logD model used by the script is provided and maintained by MMV.
Version
This integration is available to use with the latest version of StarDrop (Windows and macOS). To find out which version you have installed, start StarDrop and select the Help->About menu.
If you are using an older version of StarDrop, please contact us at support@optibrium.com and we will be happy to help install this script on your StarDrop client.
Installing the script
Windows installation
To install on Windows:
- Download the user guide
- Download the script file
- Unzip the file and open the resulting folder in Windows Explorer
- Close StarDrop if necessary
- Double-click on the file load_script.bat to run the automatic installer. The batch file will copy all the relevant files to the correct locations.
– Note: in some cases, this action may require you to override a warning from the operating system. - Start StarDrop
- A new entry named Calculate fraction unbound will appear under the Custom Scripts menu in StarDrop
- Install the models as described in Section 2.4 of the User Guide.
macOS installation
To install on macOS:
- Download the user guide
- Download the script file
- Unzip the file and open the resulting folder in Finder
- Close StarDrop if necessary
- Copy the following files and folders, creating new folders as necessary:
– binding_calculation.py to /Users/<USERNAME>/StarDrop/py3/AMG
– fractioncalculator folder to /Users/<USERNAME>/StarDrop/site-packages - Start StarDrop
- A new entry named Calculate fraction unbound will appear under the Custom Scripts menu in StarDrop
- Install the models as described in Section 2.4 of the User Guide.
We would like to acknowledge Medicines for Malaria Venture (MMV) and Mark Gardner from AMG Consultants for their contributions and assistance in developing and testing the script. The logD model used by the script is provided and maintained by MMV. This model will be updated periodically as new data become available.To run the script, open a suitable data set. Select Calculate fraction unbound under the Custom Scripts menu in StarDrop. The script will calculate predicted values for the fᵤ in hepatocytes (1 million cells/mL), microsomes (0.5mg/protein/mL), Plasma Protein Binding (PPB), or Albumax assays from other assay data, experimentally-determined logD, or calculated logD. For some calculations, results will be returned for neutral or basic compounds only. When you run the script, you will be prompted to choose which prediction you want to make. Select the value you would like to predict and click OK.
Please read the user guide for more information on how to use this script and for the complete list of available calculations.
Installation files
Windows installation
To install on Windows:
- Download the user guide
- Download the script file
- Unzip the file and open the resulting folder in Windows Explorer
- Close StarDrop if necessary
- Double-click on the file load_script.bat to run the automatic installer. The batch file will copy all the relevant files to the correct locations.
– Note: in some cases, this action may require you to override a warning from the operating system. - Start StarDrop
- A new entry named Calculate fraction unbound will appear under the Custom Scripts menu in StarDrop
- Install the models as described in Section 2.4 of the User Guide.
macOS installation
To install on macOS:
- Download the user guide
- Download the script file
- Unzip the file and open the resulting folder in Finder
- Close StarDrop if necessary
- Copy the following files and folders, creating new folders as necessary:
– binding_calculation.py to /Users/<USERNAME>/StarDrop/py3/AMG
– fractioncalculator folder to /Users/<USERNAME>/StarDrop/site-packages - Start StarDrop
- A new entry named Calculate fraction unbound will appear under the Custom Scripts menu in StarDrop
- Install the models as described in Section 2.4 of the User Guide.
How to use the script
We would like to acknowledge Medicines for Malaria Venture (MMV) and Mark Gardner from AMG Consultants for their contributions and assistance in developing and testing the script. The logD model used by the script is provided and maintained by MMV. This model will be updated periodically as new data become available.To run the script, open a suitable data set. Select Calculate fraction unbound under the Custom Scripts menu in StarDrop. The script will calculate predicted values for the fᵤ in hepatocytes (1 million cells/mL), microsomes (0.5mg/protein/mL), Plasma Protein Binding (PPB), or Albumax assays from other assay data, experimentally-determined logD, or calculated logD. For some calculations, results will be returned for neutral or basic compounds only. When you run the script, you will be prompted to choose which prediction you want to make. Select the value you would like to predict and click OK.
Please read the user guide for more information on how to use this script and for the complete list of available calculations.