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Research Catalog

Compound monograph

THIQ

THIQ is a nonpeptide small-molecule agonist at the melanocortin-4 receptor, included here as the nonpeptide comparator to the melanocortin peptides.

Published: 2026-09-13Literature/identifier verification: 2026-09-13
Melanocortin receptor ligands

01

Identity & nomenclature

THIQ is a nonpeptide small-molecule agonist at the melanocortin-4 receptor, included here as the nonpeptide comparator to the melanocortin peptides.

THIQ is ALSO the generic abbreviation for the tetrahydroisoquinoline scaffold, an entire chemical class. The generic scaffold and this defined MC4R agonist are not the same substance, and a name-only search imports unrelated chemistry — at least one supplier listing conflates them. The chlorine in the formula is a covalent aryl chloride, NOT evidence of a hydrochloride salt.

Canonical name: THIQ (MC4R agonist).

02

Molecular properties

Molecular formulaC33H41ClN6O2
Molecular mass589.18 Da
CAS Registry Number312637-48-2
PubChem CID9938402

Not a peptide. A stereodefined tetrahydroisoquinoline-carboxamide with a 4-chlorophenyl-substituted aminoacyl unit and a piperidine bearing cyclohexyl and triazolylmethyl groups, with two R-configured centres. No peptide shorthand should stand in for the structure.

03

Structural characteristics

Alanine-scanning mutagenesis at MC4R shows the nonpeptide agonists depend on residues across several transmembrane helices, while a linear peptide agonist's binding was substantially reduced by only two of the same substitutions — direct evidence that peptide and nonpeptide routes to the same receptor are not equivalent. Chimeric-receptor work identifies conserved residues required for binding and non-conserved residues in the third transmembrane helix contributing to MC4R selectivity. A receptor-bound structure places it alongside peptide agonists in the same complex study. Selectivity was examined in the comparisons tested; that is not the absence of every off-target interaction.

  • Two R-configured stereocentres
  • Aryl chloride

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

High-resolution MS should show the chlorine isotope pattern, which is the quickest confirmation that the halogen is present and covalent. NMR establishes the substituted scaffold and chiral chromatography the two stereocentres. Neither the name THIQ, nor a tetrahydroisoquinoline substructure match, nor a positive MC4R assay establishes identity — the first because the abbreviation is ambiguous, the last because other MC4R agonists give the same response.

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 mutants in binding and activation assays

    Pogozheva et al. found that the I129A mutation affected THIQ binding and potency at human MC4R in alanine-scanning assays.

    Reference [1]

  • Human MC4R/MC2R chimeras in binding and activation assays

    Yang et al. found no significant change in THIQ binding affinity or potency after replacing human MC4R transmembrane regions 2, 4, 5, or 6 with the homologous MC2R regions.

    Reference [2]

  • Human MC4R mutants in binding assays

    Yang et al. identified E100, D122, D126, F254, W258, F261, and H264 as residues important for THIQ binding in human MC4R mutagenesis assays.

    Reference [2]

  • MC4R-Gs complexes in a receptor-structure assay

    Zhang et al. reported a THIQ-stimulated full-length MC4R complex with the heterotrimeric Gs protein.

    Reference [3]

06

Verified bibliography

Cited studies by type

The 3 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

    Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists.

    Pogozheva ID, Chai BX, Lomize AL, Fong TM, Weinberg DH, Nargund RP, Mulholland MW, Gantz I, Mosberg HI

    Biochemistry · 2005-08-30 · Journal Article

    current
    PMID 16114870PMC2532597DOI 10.1021/bi0501840THIQMC1R

  2. Reference 2

    Key amino acid residues in the melanocortin-4 receptor for nonpeptide THIQ specific binding and signaling.

    Yang Y, Cai M, Chen M, Qu H, McPherson D, Hruby V, Harmon CM

    Regulatory peptides · 2009-03-20 · Journal Article

    current
    PMID 19303903PMC3216638DOI 10.1016/j.regpep.2009.03.006THIQMC1R

  3. Reference 3

    Structural insights into ligand recognition and activation of the melanocortin-4 receptor.

    Zhang H, Chen LN, Yang D, Mao C, Shen Q, Feng W, Shen DD, Dai A, Xie S, Zhou Y, Qin J, Sun JP, Scharf DH, Hou T, Zhou T, Wang MW, Zhang Y

    Cell research · 2021-08-25 · Journal Article

    current
    PMID 34433901PMC8563965DOI 10.1038/s41422-021-00552-3PT-141 (Bremelanotide)Melanotan I (Afamelanotide)alpha-MSHTHIQSetmelanotideMC1R

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
Pogozheva ID et al. 2005Study models reported: in vitro · from the abstract
Yang Y et al. 2009Study models reported: in vitro · from the abstract
Zhang H et al. 2021Study models reported: in vitro · from the abstract

Record history

Published 2026-09-13.

No changes to this record's content have been recorded since publication.

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. THIQ. Published 2026-09-13. https://purelypeptides.org/research/compounds/thiq/

10

Methodology & citation verification

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