Interactive
Every melanocortin binds more than one receptor. The question that decides whether a clean drug is even possible is how much it prefers its favourite. Pick a ligand to see its fingerprint across MC1R–MC5R — and itsselectivity window, the fold-gap between its tightest and second-tightest receptor.
Choose a ligand
broad agonist
MC3R-preferring
the only MC2R ligand
superpotent, broad
broad agonist
MC4R-preferring
MC4R drug, broad binder
blocks MC3R/MC4R
the pigment brake
Bars are sized by binding strength (p-value, on a fixed MC1R–MC5R scale);ᵐ marks a mouse value. This view has its own link — copy the address bar to share the selected ligand.
Every catalogued ligand, ranked by how cleanly it prefers one receptor — from the few genuinely selective molecules down to the broad binders that grip three or four receptors at once. Select any to see its fingerprint.
Flip the question around: for each of the five receptors, which ligands bind it — and which, if any, are selective for it.
The five melanocortin receptors read the same molecular signal — a shared His-Phe-Arg-Trp core — so a ligand shaped to fit one tends to fit the others. That is the deep reason a perfectly clean, single-receptor drug is so hard to make here, and the fingerprints show it: the natural peptides and most of the drugs sit at low windows, binding several receptors within an order of magnitude. A few stand out — bremelanotide leans clearly on MC4R, the natural brakes AgRP and agouti each prefer a single switch — but the rule is breadth, not precision. For the full argument, see why there's no clean tanning drug.
One caveat the chart cannot show: binding is not function. These bars measure how tightly a ligand holds each receptor, not what the receptor then does. Setmelanotide is the lesson — broad by binding, yet used as an MC4R medicine because its signalling is biased toward MC4R. For the qualitative agonist/antagonist picture see the receptor–ligand explorer; for every number with its citation, the binding matrix.
It is how much more tightly a ligand binds its favourite receptor than its next-favourite — the fold-gap between the tightest and second-tightest receptor. A big window (say 25×) means a relatively clean, single-target molecule; a window near 1–2× means the ligand grips several receptors almost equally and is effectively non-selective.
Because the five receptors share the same binding core (His-Phe-Arg-Trp), a ligand that fits one tends to fit the others. The fingerprints here show it directly: the natural peptides and most drugs sit at low selectivity windows, binding three or four receptors within an order of magnitude. Bremelanotide and the natural brakes are among the few with a clear single-receptor preference.
Not always. Binding is how well a ligand sticks; function is what the receptor then does. Setmelanotide is the clearest example: by raw binding it grips MC1R, MC3R and MC4R at similar strength, yet it is used as an MC4R drug because its signalling is biased toward MC4R. The fingerprint shows affinity, not the downstream signal.
Every value is the same curated affinity (pKi, pKd) or functional potency (pIC50) used across this site, from the IUPHAR/BPS Guide to Pharmacology, each traced to a primary paper. The full table with per-value citations is on the binding matrix page.
All affinity values are drawn from the IUPHAR/BPS Guide to PHARMACOLOGY (Harding SD, et al. Nucleic Acids Res.2024;52:D1438–D1449), each traced to a primary paper. The selectivity window is derived here from those values. For the complete table with a citation on every value, see the binding matrix. This is an educational resource, not medical advice — see the editorial standards.