N-isobutyryl-His-Trp-Ala-Val-D-Ala-His-Leu-NHMe (ICI 216140) a potent in vivo antaconist analogue of bombesin/gastrin releasing peptide (BN/GRP) derived from the C-terminal sequence lacking the final methionine residue

  • Life Sci. 1989;45(17):1521-7. doi: 10.1016/0024-3205(89)90417-7.
R Camble  1 ,  R Cotton ,  A S Dutta ,  A Garner ,  C F Hayward ,  V E Moore ,  P B Scholes
Affiliations
  • 1. ICI Pharmaceuticals, Alderley Park, Macclesfield, UK.
PMID: 2555638 DOI: 10.1016/0024-3205(89)90417-7
Abstract

The GRP receptor mediated growth response in Swiss 3T3 cells has been used to identify BN/GRP antagonists. Analysis of bombesin antagonism by substance P analogues and by truncated GRP analogues revealed that deletion of the C-terminal methionine residue was important for antagonism. Des-Met analogues showing potent antagonist activity in the in vitro 3T3 system (IC50 approximately 2nM) were synthesized. Further structural modification of these peptides led to the identification of (CH3)2CHCO-His-Trp-Ala-Val-D-Ala-His-Leu-NHCH3 (ICI 216140) which reduced bombesin-stimulated rat pancreatic amylase secretion to basal levels when administered subcutaneously at 2.0 mg per kg.

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