Related Experiment Video
Updated: Jun 6, 2026

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
Published on: August 17, 2019
Interpreting steep dose-response curves in early inhibitor discovery
1Department of Pharmaceutical Chemistry, University of California - San Francisco, 1700 4th Street, San Francisco, California 94158, USA. shoichet@cgl.ucsf.edu
Abstract:
Many screening hits inhibit enzymes with steep dose-response curves, which are considered pathological. Three models might explain these curves: multisite binding, an inhibitor phase transition, or stoichiometric inhibition caused by a high enzyme to Kd ratio. Experiments with promiscuous aggregators, for which steep curves are common, suggest that these curves owe to stoichiometric inhibition, which predicts that IC50 should vary linearly with enzyme concentration. Most steep dose-response curves in screening may be due to this effect.
Related Concept Videos
Drug Discovery: Overview
Dose-Response Relationship: Overview
Pharmacokinetic–Pharmacodynamic Relationship: Dose to Pharmacological Effect
Pharmacokinetic–Pharmacodynamic Relationship: Intensity of Dose-Effect Relationship
Pharmacokinetic–Pharmacodynamic Relationship: Problems
Dose Response Curve: Conventional Versus Nonmonotonic

