Peptides (New York, N.Y. : 1980), 1992-03, Vol.13 (2), p.401-407
1992
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- Autor(en) / Beteiligte
- Titel
- Metabolic stability and tumor inhibition of bombesin/GRP receptor antagonists
- Ist Teil von
- Peptides (New York, N.Y. : 1980), 1992-03, Vol.13 (2), p.401-407
- Ort / Verlag
- New York, NY: Elsevier Inc
- Erscheinungsjahr
- 1992
- Quelle
- ScienceDirect
- Beschreibungen/Notizen
- Small cell lung cancers (SCLC) synthesize and secrete bombesin/gastrin releasing peptide (BN/GRP). The autocrine growth cycle of BN/GRP in SCLC can be disrupted by BN/GRP receptor antagonists such as [Psi 13,14]BN. Here several BN analogues were solid-phase synthesized and incubated with intact SCLC cells at 37°C in RPMI medium in a time-course fashion (0–1080 minutes) to determine enzymatic stability. The proteolytic stability of the compounds was determined by subsequent HPLC analysis. The metabolic half-life ranged from 154 minutes to 1388 minutes for the six analogues studied. [Psi 13,14]BN was found to be very stable to metabolic enzymes ( T 1 2 = 646 mm ) and also inhibited SCLC xenograft formation in vivo in a dose-dependent manner. When [Psi 13,14]BN was incubated with NCI-H345 cells, it inhibited 125I-GRP binding with an IC 50 value of 30 nM. These data suggest that BN/GRP receptor antagonists such as [Psi 13,14]BN may be useful for the treatment of SCLC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0196-9781eISSN: 1873-5169DOI: 10.1016/0196-9781(92)90128-PTitel-ID: cdi_proquest_miscellaneous_73237577
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Antineoplastic Agents - metabolism, Antineoplastic Agents - pharmacology, Biological and medical sciences, Bombesin, Bombesin - metabolism, Bombesin - pharmacology, Carcinoma, Small Cell - drug therapy, Carcinoma, Small Cell - metabolism, Cell cycle, cell proliferation, Cell Division - drug effects, Cell Line, Cell physiology, Female, Fundamental and applied biological sciences. Psychology, Gastrin releasing peptide, Half-Life, Kinetics, Mice, Mice, Inbred BALB C, Mice, Nude, Molecular and cellular biology, Molecular Sequence Data, Peptides - metabolism, Peptides - pharmacology, Receptors, Bombesin, Receptors, Neurotransmitter - analysis, Receptors, Neurotransmitter - antagonists & inhibitors, Second Messenger Systems - drug effects, Small cell lung cancer, Tumor Cells, Cultured, Xenografts