Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.
Arthur A. Patchett, Ravi P. Nargund, James R. Tata et al.
Research Article — Peer-Reviewed Source
Original research published by Patchett et al. in Proceedings of the National Academy of Sciences. Redistributed under Open Access — see publisher for license terms. MedTech Research Group provides these references for informational purposes. We do not conduct original research. All studies are the work of their respective authors and institutions.
A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.
Abstract
A potent, orally active growth hormone (GH) secretagogue L-163,191 belonging to a recently synthesized structural class has been characterized. L-163,191 releases GH from rat pituitary cells in culture with EC50 = 1.3 +/- 0.09 nM and is mechanistically indistinguishable from the GH-releasing peptide GHRP-6 and the prototypical nonpeptide GH secretagogue L-692,429 but clearly distinguishable from the natural GH secretagogue, GH-releasing hormone. L-163,191 elevates GH in dogs after oral doses as low as 0.125 mg/kg and was shown to be specific in its release of GH without significant effect on plasma levels of aldosterone, luteinizing hormone, thyroxine, and prolactin after oral administration of 1 mg/kg. Only modest increases in cortisol were observed. Based on these properties, L-163,191 has been selected for clinical studies.
| DOI | 10.1073/pnas.92.15.7001 |
| PubMed ID | 7624358 |
| PMC ID | PMC41459 |
| Journal | Proceedings of the National Academy of Sciences |
| Year | 1995 |
| Authors | Arthur A. Patchett, Ravi P. Nargund, James R. Tata, M H Chen, Khaled J. Barakat, David B. Johnston, Kwan Hon Cheng, Wanda Chan, Bridget Butler, Gerard J. Hickey |
| License | Open Access — see publisher for license terms |
| Citations | 331 |