IC50

IC50 (half-maximal Inhibitory Concentration) designates the concentration of a compound required to reduce by half the activity of a biological system: enzymatic activity, radioligand binding, cell proliferation, receptor response to its natural agonist. IC50 is the counterpart of EC50 for antagonists, competitive inhibitors, negative allosteric inhibitors and cytotoxic molecules.

Like EC50, IC50 is determined by dose-response curve, but the curve takes a decreasing sigmoidal shape: the response decreases as inhibitor concentration increases. The curve's inflection point, where the response reaches 50% of its baseline value, provides the IC50 value. Assays are typically performed in the presence of a fixed concentration of reference agonist or substrate, which directly influences the obtained value.

Dependency on agonist concentration constitutes the main interpretation pitfall. For a competitive inhibitor, measured IC50 increases linearly with agonist concentration according to the Cheng-Prusoff equation: Ki = IC50 / (1 + [agonist]/EC50). This relationship enables conversion of IC50 to an absolute inhibition constant (Ki), independent of experimental context. Publishing an IC50 without specifying the agonist concentration used renders the value unusable for comparing two studies.

For non-competitive allosteric inhibitors, the relationship differs: IC50 remains stable regardless of agonist concentration but the agonist's maximum efficacy is reduced. This mechanistic distinction is established by plotting multiple agonist curves at various inhibitor concentrations and analyzing inhibition type (competitive, non-competitive, uncompetitive) through Lineweaver-Burk or Dixon plots.

In exploratory peptide research, IC50 is relevant in several contexts: receptor antagonist characterization (example: melanocortin receptor antagonists), protease inhibitors (DPP-4 inhibitors to extend endogenous GLP-1 peptide half-life), and cytotoxic peptides evaluated in experimental oncology. Available IC50 data for research compounds sold on lab-peptides-france.com enable scientific teams to position each molecule relative to its pharmacological competitors.