[Des-Met14]bombesin analogues function as small cell lung cancer bombesin receptor antagonists.
A series of bombesin (BN) analogues lacking the C-terminal methionine at the 14 position were evaluated as BN receptor antagonists. [D-Phe6]BN(6-13)amide inhibited specific 125I-GRP binding to lung cancer cell line NCI-H720 with an IC50 value of 12 nM. In contrast, [D-Phe6]BN(6-13)propylamide, butylamide and methylester were more potent with IC50 values of 3, 5 and 5 nM whereas [D-Phe6,Sta13]BN(6-13)amide was less potent with an IC50 value of 180 nM. [D-Phe6]BN(6-13)propylamide antagonized the ability of BN to elevate cytosolic Ca2+, whereas [D-Phe6]BN(6-13)butylamide was a partial agonist. In a small cell lung cancer (SCLC) growth assay, [D-Phe6]BN(6-13)propylamide inhibited colony formation. In summary, BN analogues which lack a C-terminal methionine may function as useful SCLC BN receptor antagonists.
Staley
J
J
Department of Biochemistry & Molecular Biology, George Washinton University School of Medicine and Health Sciences, Washington, DC 20037.
Coy
D
D
Taylor
J E
JE
Kim
S
S
Moody
T W
TW
D001839:Bombesin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors*; D015290:Second Messenger Systems / Q000187:drug effects; D014407:Tumor Cells, Cultured
D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D001839:Bombesin