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Compound monograph

SHU9119

SHU9119 is a cyclic lactam melanocortin analog whose receptor behaviour is subtype-dependent: antagonist at some melanocortin receptors and agonist at others. Gimenez et al. (PMID 35404053) describe SHU9119 as a cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone.

Published: 2026-09-13Last updated: 2026-10-15Literature/identifier verification: 2026-09-13
Also known asSHU-9119SHU 9119
Cyclic melanocortin analogsMelanocortin receptor ligands

01

Identity & nomenclature

SHU9119 is a cyclic lactam melanocortin analog whose receptor behaviour is subtype-dependent: antagonist at some melanocortin receptors and agonist at others. Gimenez et al. (PMID 35404053) describe SHU9119 as a cyclic heptapeptide analogue of alpha-melanocyte-stimulating hormone.

SHU9119 shares the Melanotan II ring architecture and differs by a single substitution, D-Phe to D-2-Nal, a net C4H2 or 50.0157 Da. Shared ring architecture does not mean shared pharmacological direction — see structuralNotes. Calling it 'the melanocortin blocker' conceals the central experimental limitation of the compound. PubChem CID 6440621, the entry titled Shu 9119 and the one its CAS number resolves to, encodes a different ring system; this record cites CID 9898183, which encodes the Asp2-Lys7 lactam with the same formula.

Declared aliases and development codes: SHU-9119, SHU 9119.

02

Molecular properties

Molecular formulaC54H71N15O9
Molecular mass1074.26 Da
CAS Registry Number168482-23-3
PubChem CID9898183
Three-letter sequenceNle–Asp–His–D-2-Nal–Arg–Trp–Lys
Terminal groupsN-terminal acetylation at Nle1; C-terminal amide at Lys7

Seven residues closed by a LACTAM between the Asp2 side-chain carboxyl and the Lys7 epsilon-amino group. D-2-Nal is 3-(naphthalen-2-yl)-D-alanine, one residue. No disulfide, no head-to-tail closure, and no safe linear string. Hruby et al. (PMID 7658432) write it as Ac-Nle4-c[Asp5,D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2, which places the lactam between Asp2 and Lys7 of this chain.

03

Structural characteristics

The original structure-activity work reports it as a potent MC4R antagonist and a less potent MC3R antagonist, both with minimal agonist activity, while behaving as a FULL AGONIST at MC1 and MC5 receptors. It is therefore not a pan-melanocortin antagonist, and its antagonism must not be transferred from MC4R to every experiment involving a melanocortin receptor. Receptor-bound structures exist at both MC4R — where calcium was identified as a ligand-binding cofactor — and MC1R, giving an unusually direct structural account of why one scaffold can act in opposite directions at two subtypes.

  • Asp2-Lys7 side-chain lactam
  • D-2-naphthylalanine at position 4

Ring closures: covalent bonds between residues, by position counted from the first residue of the chain.

  • Side-chain lactam Asp2–Lys7: side-chain carboxyl (Cγ) to side-chain ε-amino nitrogen (Nζ). Source numbering: Asp5–Lys10 in alpha-MSH numbering. Source: PMID 7658432.

Terminal features: N-terminal acetylation at Nle1, C-terminal amide at Lys7.

04

Molecular targets & mechanisms

Melanocortin receptors

MC1R · MC2R · MC3R · MC4R · MC5R · MCR

A family of five G protein-coupled receptors, MC1R through MC5R. ACTH recognition and signaling at MC2R depend on the accessory protein MRAP. Native hormones, peptide analogs and nonpeptide ligands differ in receptor-subtype recognition and functional direction; binding affinity, agonism and antagonism must be interpreted separately in the experimental system studied.

05

Analytical considerations

Establishing the Asp2-Lys7 lactam requires NMR or a validated orthogonal method; disulfide reduction is not a ring-opening strategy for a lactam and will not report on it. Verify D-2-Nal stereochemistry and the naphthyl attachment position. The expected mass separates SHU9119 from Melanotan II but not from every stereochemical or positional isomer, and an MC4R antagonist response is supportive functional evidence rather than chemical identification.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • Human MC4R in a receptor-structure assay

    Yu et al. reported a SHU9119-bound human MC4R structure at 2.8-angstrom resolution.

    Reference [2]

  • Human MC4R in a receptor-structure assay

    Yu et al. identified a calcium cofactor coordinated by receptor and peptide-ligand residues in the SHU9119-bound human MC4R structure.

    Reference [2]

  • MC1R-Gs complexes in a cryo-electron-microscopy assay

    Ma et al. reported a SHU9119-bound MC1R-Gs complex structure by cryo-electron microscopy.

    Reference [3]

  • Macrophages in a cAMP-accumulation assay

    Getting et al. observed that SHU9119 attenuated MTII-induced cAMP accumulation in macrophages.

    Reference [4]

Animal studies

  • Mice with crystal-induced peritonitis

    Getting et al. observed that SHU9119 did not block the antimigratory effect of KPV in mice with crystal-induced peritonitis.

    Reference [4]

06

Verified bibliography

Cited studies by type

The 5 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors.

    Hruby VJ, Lu D, Sharma SD, Castrucci AL, Kesterson RA, al-Obeidi FA, Hadley ME, Cone RD

    Journal of medicinal chemistry · 1995-09-01 · Journal Article

    current
    PMID 7658432DOI 10.1021/jm00018a005SHU9119MC1R

  2. Reference 2

    Determination of the melanocortin-4 receptor structure identifies Ca(2+) as a cofactor for ligand binding.

    Yu J, Gimenez LE, Hernandez CC, Wu Y, Wein AH, Han GW, McClary K, Mittal SR, Burdsall K, Stauch B, Wu L, Stevens SN, Peisley A, Williams SY, Chen V, Millhauser GL, Zhao S, Cone RD, Stevens RC

    Science (New York, N.Y.) · 2020-04-24 · Journal Article

    current
    PMID 32327598PMC7567314DOI 10.1126/science.aaz8995SHU9119MC1R

  3. Reference 3

    Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor.

    Ma S, Chen Y, Dai A, Yin W, Guo J, Yang D, Zhou F, Jiang Y, Wang MW, Xu HE

    Cell research · 2021-08-27 · Journal Article

    current
    PMID 34453129PMC8486761DOI 10.1038/s41422-021-00557-yMelanotan I (Afamelanotide)alpha-MSHSHU9119MC1R

  4. Reference 4

    Dissection of the anti-inflammatory effect of the core and C-terminal (KPV) alpha-melanocyte-stimulating hormone peptides.

    Getting SJ, Schiöth HB, Perretti M

    The Journal of pharmacology and experimental therapeutics · 2003-05-15 · Journal Article

    current
    PMID 12750433DOI 10.1124/jpet.103.051623alpha-MSHSHU9119KPVMelanotan IIMC1R

  5. Reference 5

    Demonstration of a Common DPhe(7) to DNal(2')(7) Peptide Ligand Antagonist Switch for Melanocortin-3 and Melanocortin-4 Receptors Identifies the Systematic Mischaracterization of the Pharmacological Properties of Melanocortin Peptides.

    Gimenez LE, Noblin TA, Williams SY, Mullick Bagchi S, Ji RL, Tao YX, Jeppesen CB, Conde-Frieboes KW, Sawyer TK, Grieco P, Cone RD

    Journal of medicinal chemistry · 2022-04-11 · Journal Article

    current
    PMID 35404053PMC9059122DOI 10.1021/acs.jmedchem.1c01295SHU9119

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Hruby VJ et al. 1995Study models reported: in vitro · from the abstract
Yu J et al. 2020Study models reported: in vitro · from the abstract
Ma S et al. 2021Study models reported: in vitro · from the abstract
Getting SJ et al. 2003Study models reported: in vitro; animal (mouse) · from the abstract
Gimenez LE et al. 2022Study models reported: in vitro · from the abstract

Record history

Published 2026-09-13.

  • : Sequence and structure
  • : Identity and nomenclature, Sequence and structure, References

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. SHU9119. Published 2026-09-13; updated 2026-10-15. https://purelypeptides.org/research/compounds/shu9119/

10

Methodology & citation verification

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