Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue.

TH9507, an analogue of human growth hormone-releasing factor (hGRF1-44NH2) minimally modified by addition of a trans-3-hexenoyl moiety to Tyr1 of the amino acid sequence, was found to be resistant to dipeptidyl aminopeptidase-IV deactivation. Compared to natural hGRF1-44NH2, the modification slowed the in vitro degradation of the peptide in rat, dog and human plasma and prolonged the in vivo plasma elimination kinetics of immunoreactive TH9507. Plasma growth hormone and insulin-like growth factor-1 (IGF-1) markedly increased in pigs, rats and dogs after daily repeat intravenous or subcutaneous injections of TH9507 at doses up to 600 microg/kg.