Resources

Signaling Kinectics

Recently there has been an explosion of interest in the kinetics / timing of signaling, enabled by biosensors of signaling. We developed equations to enable you to do curve fitting on the time course data. Plug-in equation libraries for GraphPad Prism are available for free.

Introduction & User Manual

Signaling Kinetics Analysis

How to perform signaling kinetic analysis in GraphPad Prism

Files

New Time Equation Files

Equations in GraphPad Prism template files

Training video

Youtube Workshop

Tutorial video. For practice files see links in video description

Paper

Open Access Research

Publication describing and reviewing kinetic signaling analysis.

Binding Kinetics

Binding kinetics of test compounds is often measured in competition binding assays, using the Motulsky and Mahan equation to quantify the binding rates. We have extended this equation to handle some new scenarios. First, to handle rapidly-dissociating compounds. Second, to handle new ways of setting up the assay, so you can do the experiment the way you want.

Open Access Research

Prism technical note

Extensions of the kinetics of competitive binding equation for rapid competitor kinetics or alternative assay designs

Introduction & User Manual

Rapid dissociation

How to analyze competition kinetics when the competitor dissociates rapidly

Introduction & User Manual

New Assay Formats

How to analyze competition kinetics with alternative assay designs

Allosteric Modulation

Allosteric modulation provides new dimensions of drug activity and avenues for target selectivity. Numerous investigators have derived equations for analyzing allosteric pharmacology data. We installed these equations in a free plugin for GraphPad Prism so you can use them easily.

Introduction & User Manual

Allosteric Modulator Analysis

How to perform allosteric modulator analysis in GraphPad Prism

Open Access Research

Papers Collection

Demonstrated expertise with allosteric modulator pharmacology

Files

Allosteric equations

Allosteric binding and signaling equations in GraphPad Prism template files

Binding Kinetics and PK

How do binding kinetics affect occupancy when the ligand concentration is changing over time? You can explore this with these free Excel-based simulators, without the need to learn how to use sophisticated software.

Introduction & User Manual

Binding kinetics with PK simulations

Simulate how binding kinetics and pharmacokinetics intersect to define target engagement, using Excel

Files

IV dosing simulator

IV dosing PK binding kinetic simulator

Files

Oral dosing simulator

Oral dosing PK binding kinetic simulator

Files

Repeat oral dosing simulator

Repeat oral dosing PK binding kinetic simulator

Files

With endogenous ligand simulator

Fluctuating endogenous ligand binding kinetic simulator

Assay Artifacts

Pharmacology data analysis for quantifying drug potency (Kd, EC50, Ki etc) was developed a century ago. This analysis assumes the target density is low and the assay is at equilibrium. These assumptions are often violated by new technology, e.g. in DEL and mass spec selections. See below for explainers and simulators to help you understand and manage this issue.

Files

Assay artifact simulators

Simulate how target concentration and incubation time affect your assays, using Excel

Training Video

Youtube Workshop

The Problems of Applying Classical Pharmacology to Modern Drug Discovery

Paper

Open Access Research

The Problems of Applying Classical Pharmacology Analysis to Modern In Vitro Drug Discovery Assays: Slow Binding Kinetics and High Target Concentration

Miscellaneous

Files

Sigmoid curve fitter in Excel

Analyze concentration-response data using Excel with this free simple to use program.

Files

Kinase inhibitor residence time

Analyze residence time data for kinases and other targets using this simple approach in GraphPad Prism.

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Why Choose Pharmechanics?

Pharmechanics was founded by Dr Sam Hoare in 2017, with the goal of helping pharmacologists analyze, interpret and apply their data to accelerate drug discovery and basic research on drug targets. See testimonials here to see how I can support your science.

Sam is a globally-recognized expert on industrial, applied and theoretical pharmacology. As Lead Pharmacologist at Neurocrine Biosciences, his leadership, experience and insights were instrumental in the pharmacological optimization of three novel FDA-approved therapeutics, and several more compounds in clinical development.

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