The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency.
Peschke. Bernd B; Ankersen. Michael M; Bauer. Michael M; Hansen. Thomas Kruse TK; Hansen. Birgit Sehested BS; Nielsen. Karin Kramer KK; Raun. Kirsten K; Richter. Lutz L; Westergaard. Lisbet L
Key Findings
- Adding a polar group at the C‑terminus increased potency of the secretagogue
- 4‑piperidinylamino and 4‑dimethylaminopiperidino side chains gave the most active compounds
- A lead compound showed low‑nanomolar EC50, ~40% oral bioavailability, and high GH Cmax in a swine model
Practical Outcomes
- The study points to the possibility of more potent, orally available GH secretagogues in the future, but there’s no human dosage or safety data yet. For now, biohackers should stick with established peptides like ipamorelin and watch for clinical trials of these new analogs.
Summary
Researchers tweaked the structure of growth‑hormone‑releasing peptides like ipamorelin, adding a polar group and using special piperidine‑based side chains. One of these new versions was very potent in lab tests, could be taken orally with about 40% getting into the bloodstream, and boosted growth‑hormone levels strongly in pigs. However, the work is still early‑stage and hasn’t been tested in people yet.
Abstract
In order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substituents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC(50) values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C(max) of over 40 ng mL(-1).
Study Information
pubmed
2002
10.1016/s0223-5234(02)01370-3