L-692429 (MK-0751) is a potent nonpeptidyl growth hormone secretagogue (GHS) agonist and benzolactam derivative, known for reversing glucocorticoid-induced inhibition of GH secretion. L-692429 exhibits high affinity for the G protein-coupled receptor and is useful in studying acromegaly and obesity.

CREB:60 nM (EC50), BRET:58 nM (EC50), intracellular calcium:26 nM (EC50), inositol phosphate (IP) turnover:47 nM (EC50), Serum-responsive element activity:63 nM (EC50)

L-692429, a chemical compound, activates various cellular mechanisms, including intracellular calcium release, inositol phosphate (IP) turnover, cAMP-responsive element binding protein (CREB) activity, serum-responsive element activity, and bioluminescence resonance energy transfer (BRET) activity, with EC50 values of 26 nM, 47 nM, 60 nM, 63 nM, and 58 nM, respectively[2]. In experiments involving HeLa-T4 cells, those transiently expressing flag epitope-tagged growth hormone secretagogue (GHS) receptor and treated with L-692429 show a measurable increase in intracellular calcium, as detected by fluorometry using fluo-3/AM calcium indicator dye. This response is absent in untransfected HeLa-T4 cells, indicating the specificity of L-692429 for GHS receptor-expressing cells. Moreover, L-692429 treatment significantly enhances luciferase activity in these cells, suggesting that GHS receptor activation triggers the MAPK pathway[1].

In anesthetized Wistar rats, L-756867 dose-dependently suppresses GH secretion stimulated by L-692429 (100 μg/kg), with complete inhibition achieved at an intravenous dose of 100 μg/kg of L-756867[3].