SC19 MC4R agonist lead

ID: sc19_mc4r_agonist

Aliases: SC19, setmelanotide analog, MC4R peptide agonist lead

Type: compound

Route/form: preclinical peptide lead; no established human route

Status: preclinical_lead

Evidence level: preclinical

Best data tier: direct preclinical; label comparator + adjacent early human

Support scope: human, non-human/mechanistic

Source types: human_trial, label, medicinal_chemistry

Linked sources: 3

Broad outcomes: Fat loss / metabolic health

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• MC4R agonist
• MC1R/MC3R selectivity optimization
• C-terminal lysine solubility motif

Optimization domains

• metabolic
• obesity
• appetite
• peptide design
• medicinal chemistry

Research basis

• The SC19 SAR paper directly links the lead to setmelanotide optimization: stronger MC4R potency/selectivity, improved aqueous solubility, and diet-induced-obesity mouse efficacy.
• It is useful as a medicinal-chemistry lead for the melanocortin obesity axis, not as an available intervention.
• It helps explain why selectivity over MC1R/MC3R and solubility are central problems in MC4R peptide design.

Limits, risks, and missing evidence

• SC19 has no human efficacy or safety package and should not be treated as a research-chemical protocol.
• Better receptor selectivity and solubility do not automatically solve long-term melanocortin, pigmentation, cardiovascular, or mood risks.
• Mouse obesity data are a lead-selection signal, not a performance claim.

Risk flags

• preclinical only
• medicinal chemistry lead
• mc4r
• not human ready

Linked papers, labels, and reviews

1. SAR investigation and synergistic optimization of setmelanotide yields a potent, selective, and soluble MC4R agonist
   medicinal_chemistry / pubmed_sc19_mc4r_sar_2026
   SC19 setmelanotide-analog SAR source; reports MC4R potency/selectivity, improved solubility, and diet-induced obesity mouse efficacy.
2. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency
   human_trial / pubmed_setmelanotide_pomc_lepr_phase3_2020
   Open-label phase 3 POMC/PCSK1 and LEPR deficiency trials with placebo-withdrawal design; supports rare MC4R-pathway obesity use, not common obesity.
3. DailyMed label: IMCIVREE (setmelanotide) injection
   label / dailymed_imcivree_label
   Current U.S. label for subcutaneous setmelanotide/IMCIVREE; anchors approved indications, warnings, and administration route.