The melanocortin system

The melanocortin system is a signaling network that regulates pigmentation, energy balance, inflammation, and sexual function. It operates through melanocortin receptors (MCRs), a family of five G-protein-coupled receptors (MC1R–MC5R) activated by peptides derived from pro-opiomelanocortin (POMC), such as α-MSH, β-MSH, γ-MSH, and ACTH.

Key Receptors and Their Roles

• MC1R:

  • Location: Skin, hair follicles, immune cells.

  • Function: Controls melanin synthesis (pigmentation). Variants influence skin/hair color and UV sensitivity.

• MC2R:

  • Location: Adrenal cortex.

  • Function: Binds ACTH to stimulate cortisol production (stress response, metabolism).

• MC3R:

  • Location: Hypothalamus and peripheral tissues.

  • Function: Regulates energy homeostasis, circadian rhythms, onset of puberty and inflammatory responses.

• MC4R:

  • Location: CNS (hypothalamus, brainstem).

  • Function: Critical in appetite regulation and energy expenditure; cardiovascular tone including blood pressure, mutations cause obesity.

• MC5R:

  • Location: Exocrine glands, skin, skeletal muscle.

  • Function: Influences sebaceous gland activity, immune function, and glucose uptake into muscle.

Non-selective agonists of the melanocortin receptors are approved for the the treatment of sun-hypersensitivity, rare forms of obesity and hypoactive sexual desire.

Our potent proprietary agonists bind with high affinity and are highly selective for the MC5R.

They cause robust reductions in blood glucose in models of diabetes.