Capromorelin

Growth Hormone Axis

Also known as: Entyce, AT-002, Capromorelin Tartrate, CP-424,391

Growth Hormone Secretagogues (Oral)Research phase: Phase II (human), FDA-approved (veterinary)Regulatory: FDA-approved for veterinary use (Entyce, appetite stimulation in dogs). Not approved for human use. Phase II trials showed efficacy in elderly but human development discontinued. Available as research compound.

Mechanism

Capromorelin is an oral ghrelin receptor agonist that stimulates both growth hormone release and appetite. It is notable for being the first GHS-R agonist to receive regulatory approval — though for veterinary use: it is FDA-approved as Entyce for appetite stimulation in dogs. In human clinical trials, it significantly increased GH levels, lean body mass, and functional performance in elderly subjects, but was not pursued further for human approval. It represents proof-of-concept that oral ghrelin agonists can safely boost GH in humans.

Technical detail

Capromorelin is a non-peptide, orally bioavailable growth hormone secretagogue receptor (GHS-R1a) agonist. Binds the ghrelin receptor with high affinity, mimicking endogenous ghrelin's effects on the hypothalamic-pituitary axis. Mechanism: GHS-R1a activation on pituitary somatotrophs → Gq/PLC/IP3 → intracellular calcium mobilization → GH exocytosis. Also activates hypothalamic GHRH neurons and suppresses somatostatin release. Orally bioavailable (human F ~60-70%). In a 12-month Phase II RCT in elderly subjects (65+ years): significantly increased GH secretion (2-3 fold), lean body mass (+1.4 kg), tandem walk performance, and stair climb power vs. placebo (White et al., JCEM 2009, PMID: 19567522). Appetite stimulation via vagal afferent activation and hypothalamic NPY/AgRP pathway. Veterinary approval: FDA-approved as Entyce (Aratana Therapeutics/Elanco) for inappetence in dogs.

Evidence

Capromorelin promotes weight gain in cats with unintended weight loss: a randomized, masked, placebo-controlled clinical trial
(2025) — SAGE Publications — PMID: 10.1177/1098612x251379924
Capromorelin promoted weight gain in cats with unintended weight loss due to chronic kidney disease (CKD). Over 55 days, cats given capromorelin had a mean body weight increase of +5.18% compared to a decrease of -1.65% in the placebo group.
moderate
Capromorelin increases food consumption, body weight, growth hormone, and sustained insulin-like growth factor 1 concentrations when administered to healthy adult Beagle dogs
B Zollers et al. (2017) — J Vet Pharmacol Ther — PMID: 27597271
Oral capromorelin in healthy Beagles increased food intake, body weight, transient GH, and sustained IGF-1 over 7 days; 3 mg/kg was chosen for further canine study.
moderate
Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers
Ellis AG et al. (2015) — Spinal Cord
Single-centre single ascending-dose human trial found oral capromorelin 20/50/100 mg was safe and well tolerated in both spinal cord-injured and able-bodied volunteers, with no serious adverse events and dose-dependent increases in exposure; SCI participants showed slightly delayed Tmax/half-life and greater PK variance.
moderate
Discovery and biological characterization of capromorelin analogues with extended half-lives
Carpino PA et al. (2002) — Bioorg Med Chem Lett — PMID: 12392732
Preclinical PubMed paper reports long-acting capromorelin analogues; lipophilic analogues extended canine plasma half-life, and development candidate CP-464709-18 increased IGF-1 by about 60% at 8 hours and 40% at 24 hours after repeat oral dosing in dogs, though activity varied across analogues and species.
strong

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