JMV641: a potent bombesin receptor antagonist that inhibits Swiss 3T3 cell proliferation.
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.
Azay
J
J
Laboratoire des Aminoacides, Peptides et Protéines, ESA CNRS 5075, Universités de Montpellier I, Faculté de Pharmacie, France.
Gagne
D
D
Devin
C
C
Llinares
M
M
Fehrentz
J A
JA
Martinez
J
J
D016475:3T3 Cells; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
C103208:JMV 641; D009842:Oligopeptides; D018004:Receptors, Bombesin; D018808:Transcription Factor AP-1; D000681:Amylases; D001839:Bombesin; D013936:Thymidine