Abstract
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 [Psi13,14]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. [Psi13,14]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 [Psi13,14]BN was incubated with NCI-H345 cells, it inhibited 125I-GRP binding with an IC50 value of 30 nM. These data suggest that BN/GRP receptor antagonists such as [Psi13,14]BN may be useful for the treatment of SCLC.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 401-407 |
| Number of pages | 7 |
| Journal | Peptides |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1992 |
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Keywords
- Bombesin
- Gastrin releasing peptide
- Half-life
- Small cell lung cancer
- Xenografts
ASJC Scopus subject areas
- Biochemistry
- Endocrinology
- Physiology
- Cellular and Molecular Neuroscience
Cite this
Metabolic stability and tumor inhibition of bombesin/GRP receptor antagonists. / Davis, Thomas P; Crowell, S.; Taylor, J.; Clark, D. L.; Coy, D.; Staley, J.; Moody, T. W.
In: Peptides, Vol. 13, No. 2, 1992, p. 401-407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metabolic stability and tumor inhibition of bombesin/GRP receptor antagonists
AU - Davis, Thomas P
AU - Crowell, S.
AU - Taylor, J.
AU - Clark, D. L.
AU - Coy, D.
AU - Staley, J.
AU - Moody, T. W.
PY - 1992
Y1 - 1992
N2 - 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 [Psi13,14]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. [Psi13,14]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 [Psi13,14]BN was incubated with NCI-H345 cells, it inhibited 125I-GRP binding with an IC50 value of 30 nM. These data suggest that BN/GRP receptor antagonists such as [Psi13,14]BN may be useful for the treatment of SCLC.
AB - 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 [Psi13,14]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. [Psi13,14]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 [Psi13,14]BN was incubated with NCI-H345 cells, it inhibited 125I-GRP binding with an IC50 value of 30 nM. These data suggest that BN/GRP receptor antagonists such as [Psi13,14]BN may be useful for the treatment of SCLC.
KW - Bombesin
KW - Gastrin releasing peptide
KW - Half-life
KW - Small cell lung cancer
KW - Xenografts
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UR - http://www.scopus.com/inward/citedby.url?scp=0026637732&partnerID=8YFLogxK
U2 - 10.1016/0196-9781(92)90128-P
DO - 10.1016/0196-9781(92)90128-P
M3 - Article
VL - 13
SP - 401
EP - 407
JO - Peptides
JF - Peptides
SN - 0196-9781
IS - 2
ER -