BW 1023U90: a new GRP receptor antagonist for small-cell lung cancer cells.

Abstract

Gastrin-releasing peptide (GRP) receptor antagonists were synthesized and their ability to interact with small-cell lung cancer (SCLC) cells determined. [125I] BW1023U90, bound with high affinity (Kd = 2 nM) to a single class of sites (Bmax = 55 fmol/mg protein) using SCLC cell line NCI-H345. [125I] BW1023U90 binding was time dependent and reversible even at 37 degrees C as the ligand was minimally internalized. Specific [125I] BW1023U90 binding was inhibited with high affinity by GRP as well as bombesin (BB) but not neuromedin B (NMB). BW1023U90 inhibited the ability of BB to elevate cytosolic Ca2+ and increase the growth of SCLC cells. A BW1023U90 analogue, BW2258U89 (10 micrograms/day, SC) slowed SCLC xenograft format on in nude mice and [125I] BW 1023U90 localized to SCLC tumors 1 h after injection into nude mice. BW2258U89 (4% by weight) was placed in microspheres and slowly released over a 3-week period in nude mice bearing SCLC xenografts. The microspheres containing BW2258U89 strongly inhibited SCLC growth in vivo. A radioimmunoassay was developed for the GRP receptor antagonists and the rabbit antiserum cross-reacted totally with BW2258U89 or BW1023U90. BW2258U89 immunoreactivity (5 nM) was detected in the plasma of nude mice containing the microspheres after 1 week. These data suggest that GRP receptor antagonists bind to receptors on SCLC tumors.

• Authors: T W Moody, R Venugopal, V Hu, Y Gozes, J McDermed, J J Leban
• Journal: Peptides (Peptides) Vol. 17 Issue 8 Pg. 1337-43 ( 1996) ISSN: 0196-9781 [Print] United States
• PMID: 8971929 (Publication Type: Journal Article)

Chemical References

• BW 1023U90
• Oligopeptides
• Peptides
• Receptors, Bombesin
• Gastrin-Releasing Peptide

Topics

• Amino Acid Sequence
• Animals
• Carcinoma, Small Cell (drug therapy, metabolism, pathology)
• Gastrin-Releasing Peptide
• Humans
• Kinetics
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Oligopeptides (chemistry, metabolism, pharmacology)
• Peptides (chemistry, metabolism, pharmacology)
• Receptors, Bombesin (antagonists & inhibitors)
• Structure-Activity Relationship
• Transplantation, Heterologous
• Tumor Cells, Cultured