Potential MOA

Understanding the potential MOA of Acthar Gel

Acthar Gel vial

Acthar Gel is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides.1

While the exact mechanism of action of Acthar Gel is not fully understood, further investigation is being conducted. This information is based on nonclinical and pharmacodynamic data, and the relationship to clinical benefit is unknown.

Watch Principal Research Pharmacologist Dale Wright, PhD, explain the potential MOA of Acthar Gel

Dale Wright MOA video player: Ch. 1: Introduction

MELANOCORTIN RECEPTOR ENGAGEMENT

Acthar Gel engages melanocortin receptors (MCRs) expressed on immune cells and other tissues throughout the body and is thought to produce both an indirect anti-inflammatory effect and a direct cell effect2-6

Acthar Gel is thought to engage multiple systems in the body to modulate cellular functions

In the body, MC2Rs are primarily expressed on the adrenal cortex and the engagement of these receptors leads to the production of cortisol. The other MCRs are found on immune and other cells throughout the body. They play a key role in regulating inflammation and other cellular functions.2

In an in vitro study where the relative functional potency of MCRs was measured, 6% of Acthar Gel’s relative functional potency occurred at MC2R. The remaining 94% occurred at the other MCRs.3

Relative Functional Potency at MCRs3,7

*Acthar Gel was tested in vitro for its ability to increase cellular cAMP concentrations in whole cell cultures.

cAMP=cyclic adenosine monophosphate; MCR=melanocortin receptor. 

Study design3,7

Cell cultures expressing endogenous MC1R and cloned human MC2R, MC3R, MC4R, and MC5R were treated with Acthar Gel. The increase in cellular cAMP (cyclic adenosine monophosphate) concentration was assayed. Agonist activity was determined using nonlinear regression analysis of the concentration response curves. Relative functional potency was determined by calculating the log of each half maximal effective concentration (EC50) value, summing EC50 values, and determining the percentage of the total for each receptor. Receptor densities and the induction of cAMP are assumed to be equivalent for all receptors.

While the exact mechanism of action of Acthar Gel is not fully understood, further investigation is being conducted. This information is based on nonclinical and pharmacodynamic data, and the relationship to clinical benefit is unknown.