A Nonpeptidyl Growth Hormone Secretagogue

A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-{[2′-(1 H-tetrazol-5-yl) (1, 1′-biphenyl)-4-yl]methyl}-1 H-1-benzazepin-3(R)-yl)-butanamide (L-692,429) has been identified. L-692, 429 synergizes with the natural growth hormone secretagogu...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1993-06, Vol.260 (5114), p.1640-1643
Main Authors: Smith, Roy G., Cheng, Kang, Schoen, William R., Pong, Sheng-Shung, Hickey, Gerard, Jacks, Tom, Butler, Bridget, Wanda W.-S. Chan, Chaung, Lee-Yuh P., Judith, Fred, Taylor, Joyce, Wyvratt, Matthew J., Fisher, Michael H.
Format: Article
Language:English
Subjects:
Agonists
Amino Acid Sequence
Animals
Benzazepines - pharmacology
Biological and medical sciences
Cells, Cultured
Depolarization
Dogs
Enantiomers
Fluorescence
Growth Hormone - drug effects
Growth Hormone - metabolism
Growth hormones
Hormones
Hormones. Endocrine system
Imaging
Ligands
Male
Medical research
Medical sciences
Membrane Potentials - drug effects
Molecular Sequence Data
Molecules
Oligopeptides - chemistry
Oligopeptides - pharmacology
Pharmacology. Drug treatments
Physical growth
Pituitary Gland, Anterior - drug effects
Pituitary Gland, Anterior - metabolism
Rats
Rodents
Second Messenger Systems - drug effects
Secretion
Somatotropin
Stereoisomerism
Structure-Activity Relationship
Tetrazoles - pharmacology
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Description
Summary:A nonpeptidyl secretagogue for growth hormone of the structure 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-{[2′-(1 H-tetrazol-5-yl) (1, 1′-biphenyl)-4-yl]methyl}-1 H-1-benzazepin-3(R)-yl)-butanamide (L-692,429) has been identified. L-692, 429 synergizes with the natural growth hormone secretagogue growth hormone-releasing hormone and acts through an alternative signal transduction pathway. The mechanism of action of L-692,429 and studies with peptidyl and nonpeptidyl antagonists suggest that this molecule is a mimic of the growth hormone-releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH$_2$ (GHRP-6). L-692,429 is an example of a nonpeptidyl specific secretagogue for growth hormone.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.8503009