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Discovery of Capromorelin: An Orally Active GH Secretagogue With High Potency and Bioavailability

RPEP-008012003Carpino, Philip A; Lefker, Bruce A; Toler, Steven M; Pan, Lydia C; Hadcock, John R; Cook, Ewell R; DiBrino, Joseph N; Campeta, Anthony M; DeNinno, Shari L; Chidsey-Frink, Kristin L; Hada, William A; Inthavongsay, John; Mangano, F Michael; Mullins, Michelle A; Nickerson, David F; Ng, Oicheng; Pirie, Christine M; Ragan, John A; Rose, Colin R; Tess, David A; Wright, Ann S; Yu, Li; Zawistoski, Michael P; DaSilva-Jardine, Paul A; Wilson, Theresa C; Thompson, David D
Animal StudyPreliminary evidence
The takeaway

Capromorelin (CP-424,391), a novel pyrazolinone-piperidine dipeptide, showed potent GH-releasing activity with 60% oral bioavailability in dogs and significant GH/IGF-1 elevation in rats, advancing toward clinical development.

60% oral bioavailability

Capromorelin achieved 60% oral bioavailability in dogs — exceptional for a GH-releasing compound, making practical oral GH therapy feasible

What the researchers found

Capromorelin showed potent GHS-R binding (Ki=7 nM), oral GH-releasing activity in rats, 60% oral bioavailability in dogs, and IGF-1 elevation with repeated dosing, emerging as a clinical development candidate.

Why it matters

An oral GH secretagogue with 60% bioavailability is exceptional. This drug-like profile makes oral GH therapy practical, potentially replacing GH injections.

How the study worked

Preclinical study with GHS-R binding assays, in-vitro pituitary cell GH release, in-vivo GH/IGF-1 measurement in rats, and pharmacokinetic analysis in dogs.

What this study cannot tell us

Preclinical data only. Dog bioavailability may not predict human PK. Long-term safety not assessed.

How to read the evidence

Preliminary preclinical evidence with comprehensive pharmacology and pharmacokinetics across multiple species.

When this study was published

Published in 2003. Capromorelin has since been developed and approved as an oral GH secretagogue for veterinary use (dogs) under the brand name Entyce.

The bigger picture

Achieving high oral bioavailability for a peptide-mimetic drug is a major pharmaceutical achievement. Capromorelin's success validates the non-peptide GH secretagogue approach.

Questions still open

  • Does capromorelin maintain efficacy with chronic dosing?
  • What is its selectivity profile?
  • Will the high oral bioavailability translate to humans?

Common questions

What is capromorelin?
It's an oral GH-releasing drug with excellent absorption (60% bioavailability). Originally developed for human use, it's now approved as a veterinary drug (Entyce) for stimulating appetite and GH in dogs.
Why is 60% bioavailability important?
Most peptide-like drugs are barely absorbed orally (single-digit percentages). Achieving 60% means most of the pill actually reaches the bloodstream — making oral dosing reliable and predictable.

Read the original research

Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.

Bioorganic & medicinal chemistry, 11(4), 581-90

View on PubMed ↗

Citation

Carpino, Philip A; Lefker, Bruce A; Toler, Steven M; Pan, Lydia C; Hadcock, John R; Cook, Ewell R; DiBrino, Joseph N; Campeta, Anthony M; DeNinno, Shari L; Chidsey-Frink, Kristin L; Hada, William A; Inthavongsay, John; Mangano, F Michael; Mullins, Michelle A; Nickerson, David F; Ng, Oicheng; Pirie, Christine M; Ragan, John A; Rose, Colin R; Tess, David A; Wright, Ann S; Yu, Li; Zawistoski, Michael P; DaSilva-Jardine, Paul A; Wilson, Theresa C; Thompson, David D. (2003). Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.. Bioorganic & medicinal chemistry, 11(4), 581-90.