Tabimorelin

Growth Hormone / Recovery

Also known as: NN703, Tabimorelin Hydrochloride

Growth Hormone SecretagoguesResearch phase: Phase 2 (discontinued)Regulatory: Not approved. Development discontinued by Novo Nordisk.

Mechanism

Tabimorelin is an oral growth hormone secretagogue that was developed by Novo Nordisk. It stimulates the pituitary to release growth hormone by activating the ghrelin receptor, similar to MK-677 but with a different chemical structure. Phase 2 trials in GH-deficient adults showed GH increases, but development was discontinued.

Technical detail

Tabimorelin (NN703) is a synthetic peptidomimetic GHS-R1a agonist with oral bioavailability. It mimics ghrelin binding at the growth hormone secretagogue receptor, activating Gq-PLC-IP3 signaling on anterior pituitary somatotrophs to increase pulsatile GH release. Unlike MK-677 (a benzolactam), tabimorelin has a distinct spiroindanylpiperidine structure. Phase 2 data showed significant GH and IGF-1 elevation in GH-deficient adults but development was halted.

Evidence

Adipogenic and orexigenic effects of the ghrelin-receptor ligand tabimorelin are diminished in leptin-signalling-deficient ZDF rats.
Holm AM, Johansen PB, Ahnfelt-Rønne I, Rømer J. (2004) — Eur J Endocrinol — PMID: 15191361
Tabimorelin, a ghrelin-receptor ligand, induced hyperphagia and adiposity in lean control rats but not in leptin-signaling-deficient ZDF rats. It altered the expression of certain neuropeptides in the hypothalamus, suggesting a mechanism for its effects that depends on intact leptin-receptor signaling.
emerging
Oral administration of the growth hormone secretagogue NN703 in adult patients with growth hormone deficiency.
Svensson J et al. (2003) — Clin Endocrinol (Oxf) — PMID: 12699438
Randomized multicenter study in adult growth hormone deficiency supported biologic activity of oral tabimorelin/NN703 and provided early patient-level safety data.
moderate
The pharmacokinetics, pharmacodynamics, safety and tolerability following 7 days daily oral treatment with NN703 in healthy male subjects.
Zdravkovic M et al. (2001) — Growth Horm IGF Res — PMID: 11437473
Short healthy-volunteer study showed oral tabimorelin (NN703) produced expected GH-axis pharmacodynamic activity with tolerability suitable for early clinical development.
moderate
The pharmacokinetics, pharmacodynamics, safety and tolerability of a single dose of NN703, a novel orally active growth hormone secretagogue in healthy male volunteers.
Zdravkovic M, Søgaard B, Ynddal L, Christiansen T, Agersø H, Thomsen MS, Falch JE, Ilondo MM. (2000) — Growth Horm IGF Res — PMID: 11032702
The study found that NN703 (tabimorelin) significantly increased GH AUC and C(max) at doses of 3.0, 6.0, and 12 mg/kg compared to placebo. IGF-1 levels were also significantly increased at doses of 6.0 and 12.0 mg/kg. The study suggests that NN703 is a promising candidate for treating GH deficiency/insufficiency.
moderate

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