Metabolic stability and tumor inhibition of bombesin/GRP receptor antagonists

T. P. Davis, S. Crowell, J. Taylor, D. L. Clark, D. Coy, J. Staley, T. W. Moody

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Small cell lung cancers (SCLC) synthesize and secrete bombesin/gastrin releasing peptide (BN/GRP). The autocrine growth cycle of BN/GRP in SCLC can be disrupted by BN/GRP receptor antagonists such as [Psi13,14]BN. Here several BN analogues were solid-phase synthesized and incubated with intact SCLC cells at 37°C in RPMI medium in a time-course fashion (0-1080 minutes) to determine enzymatic stability. The proteolytic stability of the compounds was determined by subsequent HPLC analysis. The metabolic half-life ranged from 154 minutes to 1388 minutes for the six analogues studied. [Psi13,14]BN was found to be very stable to metabolic enzymes (T 1 2 = 646 mm) and also inhibited SCLC xenograft formation in vivo in a dose-dependent manner. When [Psi13,14]BN was incubated with NCI-H345 cells, it inhibited 125I-GRP binding with an IC50 value of 30 nM. These data suggest that BN/GRP receptor antagonists such as [Psi13,14]BN may be useful for the treatment of SCLC.

Original languageEnglish (US)
Pages (from-to)401-407
Number of pages7
JournalPeptides
Volume13
Issue number2
DOIs
StatePublished - Jan 1 1992

Keywords

  • Bombesin
  • Gastrin releasing peptide
  • Half-life
  • Small cell lung cancer
  • Xenografts

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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    Davis, T. P., Crowell, S., Taylor, J., Clark, D. L., Coy, D., Staley, J., & Moody, T. W. (1992). Metabolic stability and tumor inhibition of bombesin/GRP receptor antagonists. Peptides, 13(2), 401-407. https://doi.org/10.1016/0196-9781(92)90128-P