| Literature DB >> 1329046 |
T P Davis1, S Crowell, J Taylor, D L Clark, D Coy, J Staley, T W Moody.
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 degrees 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 (T1/2 = 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.Entities:
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Year: 1992 PMID： 1329046 DOI： 10.1016/0196-9781(92)90128-p
Source DB: PubMed Journal: Peptides ISSN： 0196-9781 Impact factor: 3.750