JMV641: a potent bombesin receptor antagonist that inhibits Swiss 3T3 cell proliferation

Regul Pept. 1996 Aug 27;65(1):91-7. doi: 10.1016/0167-0115(96)00077-8.


The peptides of the bombesin family are involved in stimulation of mitogenesis in various cell lines, including cancerous cell lines. Bombesin receptor antagonists are of great interest to inhibit this proliferation. We have synthesized a potent bombesin receptor antagonist, e.g., compound JMV641 [H-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-*CH[CH2-CH(CH3)2]-**CHOH- (CH2)3-CH3 [*(S); **92% of (S) isomer], in which a pseudopeptide bond mimicking the transition state analogue replaced the peptide bond between the two C-terminal residues. This compound was highly potent to dose-dependently inhibit binding of 125I-GRP to Swiss 3T3 cells (IC50 = 0.85 +/- 0.15 nM) and bombesin-stimulated Swiss 3T3 proliferation (pA2 = 8.78). However, compound JMV641 can inhibit bombesin-induced AP-1 regulated genes that are nuclear messengers mediating the actions of signal transduction pathways stimulated by growth factors.

MeSH terms

  • 3T3 Cells
  • Amylases / metabolism
  • Animals
  • Bombesin / pharmacology
  • Cell Division / drug effects
  • Gene Expression Regulation / drug effects
  • Mice
  • Oligopeptides / pharmacology*
  • Receptors, Bombesin / antagonists & inhibitors*
  • Signal Transduction
  • Thymidine / metabolism
  • Transcription Factor AP-1 / metabolism


  • JMV 641
  • Oligopeptides
  • Receptors, Bombesin
  • Transcription Factor AP-1
  • Amylases
  • Bombesin
  • Thymidine