Vault Snack #30 – Additional Curve Fits for Plotting and Analysing Assay Data in CDD Vault

Hello, CDD users! As we move into the summer months, we’d like to share with you COOL new additions to the CDD Vault Curves feature set.

These features include curve fits such as:

• Bell Equation
• Linear Equation
• Scatter Plot and Line Graph
• Exponential Decay
• Biphasic Equation
• Enzyme Kinetics: Michaelis-Menten Equation
• Exponential Accumulation and Decay Equation
• Hill Equation
• PK Intravenous Dosing: Exponential Decay Equation
• PK Oral Dosing: Exponential Accumulation and Decay Equation
• Receptor Binding: One Site Total Binding

This ever expanding list will allow you to plot a wider range of assay data using CDD Vault. Other recent enhancements include Area Under Curve (AUC) calculation, plot customization, and export options. 

As a quick recap, the Curves add-on offers additional features for plotting and analysing data within CDD Vault. In order to use these new curve fits, they need to be first enabled in your Vault by CDD Support and then your Vault administrator can choose which Curves to allow in a given Vault by navigating to the Settings > Vault > Plots page. 

If you are not yet subscribed to Curves, please contact your CDD Account Manager, or CDD Support, to discuss enabling these features in your Vault.

Some of the most recent enhancements to the CDD Vault Curves add-on include the Pharmacokinetic (PK) IV and Oral curve fits.

PK Intravenous Dosing: Exponential Decay Equation

Intravenous (IV) dosing refers to the administration of a drug directly into the bloodstream by injection (bolus) or continuous infusion. This is a favored route to dose test articles given its straightforward nature as compounds bypass first-pass metabolism and enter systemic circulation instantaneously and completely. This can be a great method to gauge efficacy or target engagement before tuning oral bioavailability or to better understand toxicity at very high exposures of the compound. The following parameters will automatically be calculated by CDD Vault for this plot type:

• C0 - concentration at zero time
• Cmin - concentration at infinite time
• Ke - elimination rate constant
• T1/2 - half-life (ln(2)/Ke)
• Tau - mean life time (1/Ke)
• AUC - area under curve in observed interval (0, t)
• AUCt-inf - extrapolated AUC after last measurement (Cmin / Ke)
• AUC0-inf - extrapolated total area under the curve (AUC + AUCt-inf)
• Plateau = Cmin
• Span - C0 - Cmin
• N - total number of data points used to perform the curve fit
• R-squared

PK Oral Dosing: Exponential Accumulation and Decay Equation

In the context of drug discovery and pharmacokinetics, exponential accumulation and decay curve fitting is used to model how drug concentrations change over time within a biological system. This approach is essential for understanding drug absorption, distribution, metabolism, and elimination (ADME). This particular curve fit aims to model both the accumulation (absorption) and decay (elimination) phases of an oral drug dose in a biological system. The following parameters will automatically be calculated by CDD Vault for this plot type:

• C - amplitude
• Cmax - highest measured concentration after the absorption phase
• Cmin - lowest measured concentration after the elimination phase
• Ka - absorption phase rate constant
• Ke - elimination phase rate constant
• T½ - half-life (ln(2)/Ke)
• Tmax - time where Cmax is reached
• AUC - area under curve in observed interval (0, t)
• AUCt-inf - extrapolated AUC after last measurement (Cmin (1/Ke - 1/Ka))
• AUC0-inf - extrapolated total area under the curve (AUC + AUCt-inf)
• N - total number of data points used to perform the curve fit
• Maximum measured - Maximum extremal value of all measured responses
• Minimum measured - Minimum extremal value of all measured responses
• R-squared - quality of fit

Helpful Tips and tricks for getting the best out of curves:

• Set up Curve Comments from the Vault Settings to quickly QC data and communicate within your team. A unique list of curve comments can be added for each curve fit.

• Tailor plot appearances by customizing X and Y axes for each plot type, including ranges and logarithmic/linear scales.

• Note the ability to use calculated readouts (e.g. HTRF ratios and background subtraction) on the plot axis, and the ability to create multiple plots per protocol.

• Once you have your data plotted, you can choose to export it as a png or a pdf. The Curves Add-On allows you to customize this export further, such as adding a title to your plot, modifying the axis labels, and determining what should be included in the legend.

• Area Under the Curve is now available as a default calculated parameter for appropriate curve fits. The AUC will be calculated automatically and available by clicking Customize Your Report and selecting ‘Area under the curve’ from the protocol readout definition section.

• Fold change is another useful parameter when evaluating your results in CDD Vault. If you’ve included a reference compound in your plate map, the fold change is the ratio of the test compound to the reference compound. It's displayed for calculated intercepts (e.g., EC50, EC90) and Area Under the Curve, per plate or run, based on protocol definition.

Additional curve fits are coming, let us know if there are particular curves you would like CDD to consider prioritizing. Stay tuned for future Vault updates. 

CDD Support is always happy to schedule a working session to help you get familiar with these features in CDD Vault. Just email CDD Support to schedule your feature review!

If this Vault Snack leaves you hungry for more, all previous Vault Snacks can be found here and as always, feel free to contact CDD Support — we are available to help you succeed in using CDD Vault.