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Therapeutic Class Review · Melanocortin System

Melanocortin Agonist
Research Hub

Exploring MC1R–MC5R receptor agonists — from FDA-approved therapeutics to next-generation candidates. 3 approved therapies · 5 receptor subtypes · expanding pipeline.

3FDA-Approved Therapies
5Receptor Subtypes
3+Pipeline Candidates

Approved Therapeutics

FDA-Approved Melanocortin Agonists

Three approved therapies targeting the melanocortin system across distinct therapeutic indications

Setmelanotide

FDA 2020

IMCIVREE

MC4R

Indication: Obesity from POMC, PCSK1, or LEPR deficiency

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Bremelanotide

FDA 2019

Vyleesi / PT-141

MC4R + MC1R

Indication: Hypoactive sexual desire disorder in premenopausal women

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Afamelanotide

FDA 2019

Scenesse

MC1R

Indication: Erythropoietic protoporphyria phototoxicity

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Receptor Biology

Melanocortin Receptor Map

Five distinct receptor subtypes with different tissue distributions, functions, and therapeutic development status

Approved
Clinical Trials
Preclinical
MC1RApproved

Location

Skin, melanocytes, immune cells

Function

Pigmentation (eumelanin synthesis), UV protection, immune modulation

Key agonist

Afamelanotide (Scenesse)

MC2RPreclinical

Location

Adrenal cortex

Function

Adrenal steroidogenesis — sole known receptor for ACTH

Key agonist

None approved

MC3RClinical Trials

Location

Brain, gut, immune cells

Function

Energy homeostasis, anti-inflammatory signaling, feeding behavior

Key agonist

Under investigation

MC4RApproved

Location

Hypothalamus, limbic system

Function

Appetite, energy expenditure, sexual function, autonomic control

Key agonist

Setmelanotide, Bremelanotide

MC5RPreclinical

Location

Exocrine glands, skin, skeletal muscle

Function

Exocrine secretion, sebum production, immune function

Key agonist

None approved

Receptor Binding Selectivity Profiles

Relative binding activity across MC1R–MC5R for each FDA-approved agonist

Normalized relative values (0–100) for visualization only — not exact Ki or EC50 data.

Emerging Candidates

Melanocortin Agonist Pipeline

Next-generation candidates advancing toward and through clinical development as of May 2026

◎ Planned

PL7737

Palatin Technologies

Obesity

MC4ROral small moleculePhase 1 planned 2026
◎ Planned

Next-gen MC4R peptide agonists

Palatin Technologies

Hypothalamic obesity

MC4ROnce-weekly subcutaneous peptidePhase 1 mid-2026
● Active

Setmelanotide (expanded indications)

Rhythm Pharmaceuticals

Additional genetic obesity subtypes

MC4RDaily subcutaneousPhase 3 ongoing

Platform Tools

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