Discovery of Capromorelin: An Orally Active GH Secretagogue With High Potency and Bioavailability
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.
Quick Facts
What This Study 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.
Key Numbers
How They Did This
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.
Why This Research Matters
An oral GH secretagogue with 60% bioavailability is exceptional. This drug-like profile makes oral GH therapy practical, potentially replacing GH injections.
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.
What This Study Doesn't Tell Us
Preclinical data only. Dog bioavailability may not predict human PK. Long-term safety not assessed.
Questions This Raises
- ?Does capromorelin maintain efficacy with chronic dosing?
- ?What is its selectivity profile?
- ?Will the high oral bioavailability translate to humans?
Trust & Context
- Key Stat:
- 60% oral bioavailability Capromorelin achieved 60% oral bioavailability in dogs — exceptional for a GH-releasing compound, making practical oral GH therapy feasible
- Evidence Grade:
- Preliminary preclinical evidence with comprehensive pharmacology and pharmacokinetics across multiple species.
- Study Age:
- Published in 2003. Capromorelin has since been developed and approved as an oral GH secretagogue for veterinary use (dogs) under the brand name Entyce.
- Original Title:
- Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.
- Published In:
- Bioorganic & medicinal chemistry, 11(4), 581-90 (2003)
- Authors:
- 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
- Database ID:
- RPEP-00801
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked 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 More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-00801APA
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.
MLA
Carpino, Philip A, et al. "Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin.." Bioorganic & medicinal chemistry, 2003.
RethinkPeptides
RethinkPeptides Research Database. "Pyrazolinone-piperidine dipeptide growth hormone secretagogu..." RPEP-00801. Retrieved from https://rethinkpeptides.com/research/carpino-2003-pyrazolinonepiperidine-dipeptide-growth-hormone
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.