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Study · In vitro (cells) · 2026

3 results

The kisspeptin analog C6 elicits greater tachyphylaxis and transcriptional activation than kisspeptin-10 and -54.

Robert V, Lomet D, Dardente H, Aucagne V, Beltramo M

Molecular and cellular endocrinology30 Jun 2026

PMID42379494 (opens in a new tab)DOI10.1016/j.mce.2026.112854 (opens in a new tab)PepBankPUB-42379494
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Summary

The discovery of the neuropeptide kisspeptin (Kp) and its receptor has attracted considerable attention as a potential therapeutic target for the treatment of various medical disorders and for the management of reproduction in livestock. To this end, endogenous agonists (hKp10 and hKp54) as well as synthetic agonists (TAK-448 and C6) have been evaluated in vivo with promising results. However, direct comparative data on the effects of these molecules remain limited, both in vivo and in vitro. Given the importance of such comparisons from a drug discovery perspective, we sought to characterize and directly compare the in vitro pharmacological profiles of hKp10, hKp54, and C6. Using HEK293 cells stably expressing the human Kp receptor, we found that C6 produced the most sustained intracellular Ca2+ mobilization. This prolonged signaling was associated with more pronounced tachyphylaxis, which we propose results from a greater depletion of intracellular Ca2+ stores. In contrast, a second stimulation with low concentrations of hKp54, but not of hKp10, elicited an increased response. We also assessed the expression of a selected panel of genes at different time points following treatment. C6 induced the strongest and most sustained transcriptional response, followed by hKp54 and hKp10. Notably, marked upregulation was observed for immediate-early genes (IER2, EGR1, and KLF10), transcription factors (NR4A1, NR4A2, and NFKB1A), and inflammatory mediators (CXCL8, CXCL1, and CCL2). Collectively, these findings demonstrate distinct in vitro pharmacological profiles among the three agonists. Such differences may have important implications for therapeutic efficacy and the potential induction of adverse effects during drug development.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Activity measurement

    In HEK293 cells expressing the human Kp receptor, hKp10 produced less sustained intracellular Ca2+ mobilization than the analog C6, which was the most sustained.

    In plain wordsIn lab cells, hKp10 gave a shorter calcium signal than the kisspeptin analog C6.

    Peptide
    Kisspeptin-10
    Outcome
    DecreaseSustained intracellular Ca2+ mobilization
    Study

    humann: not reported in source

    HEK293 cells stably expressing the human Kp receptor
    Comparator
    C6
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Using HEK293 cells stably expressing the human Kp receptor, we found that C6 produced the most sustained intracellular Ca2+ mobilization.
    1 context sentence
    Summary · context
    Given the importance of such comparisons from a drug discovery perspective, we sought to characterize and directly compare the in vitro pharmacological profiles of hKp10, hKp54, and C6.
  2. 02LabIn vitro (cells)Activity measurement

    In HEK293 cells, a second stimulation with low concentrations of hKp10 did not elicit an increased response, unlike hKp54.

    In plain wordsIn lab cells, a second low dose of hKp10 did not give a bigger response, unlike hKp54.

    Peptide
    Kisspeptin-10
    Outcome
    No significant changeResponse to a second stimulation (tachyphylaxis)
    Study

    humann: not reported in source

    HEK293 cells stably expressing the human Kp receptor
    Comparator
    hKp54
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In contrast, a second stimulation with low concentrations of hKp54, but not of hKp10, elicited an increased response.
    1 context sentence
    Summary · context
    Using HEK293 cells stably expressing the human Kp receptor
  3. 03LabIn vitro (cells)Mechanism

    In HEK293 cells, hKp10 induced a transcriptional response that was weaker than that of hKp54 and C6.

    In plain wordsIn lab cells, hKp10 switched on genes less strongly than hKp54 and the analog C6.

    Peptide
    Kisspeptin-10
    Outcome
    DecreaseTranscriptional response
    Study

    humann: not reported in source

    HEK293 cells stably expressing the human Kp receptor
    Comparator
    C6 and hKp54
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    C6 induced the strongest and most sustained transcriptional response, followed by hKp54 and hKp10.
    1 context sentence
    Summary · context
    Using HEK293 cells stably expressing the human Kp receptor

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Version history

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  1. Version 2Current

    10 Oct 2026, 09:43 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:04 UTC

    First added · source update from Europe PMC

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