Bombesin antagonist
IC50: 10.4 nM for rat pancreas; 2.4 nM for Guinea pig pancreas
Bombesin has common effects on the gastrointestinal tract and feeding behavior. Bombesin acts on two types of receptors: one with high affinity for neuromedin B and another with high affinity for bombesin and gastrin-releasing peptide (GRP). BIM 189 is a a new peptide of bombesin antagonis, while BIM 187 is a bombesin agonist.
In vitro: BIM 189 was one of the most potent bombesin antagonists known in the guinea pig and 3T3 cell systems but has 40% partial agonist activity in the rat. Loss of agonism might be attributed to the Cl electron withdrawing effects rather than the size of the Cl since far larger Na114 substitutions did not effect agonist activity [2].
In vivo: BIM 187 at 4 μg/kg, significantly reduced food intake at 30 min in rat, but did not change the total 6-h food intake. BIM 189 (10 mg/kg), had no effect on food intake when administered alone, even at high doses (20 mg/kg). BIM 189 selectively reduced bombesin-induced satiety but had no effect on satiety induced by BIM 187[2].
Clinical trial: Up to now, BIM 189 is still in the preclinical development stage.
Reference:
[1] Coy D, Wang LH, Jiang NY, Jensen R.? Short chain bombesin pseudopeptides with potent bombesin receptor antagonist activity in rat and guinea pig pancreatic acinar cells. Eur J Pharmacol. 1990 Nov 6;190(1-2):31-8.
[2] Laferrère B,?Leroy F,?Bonhomme G,?Le Gall A,?Basdevant A,?Guy-Grand B.? Effects of bombesin, of a new bombesin agonist (BIM 187) and a new antagonist (BIM 189) on food intake in rats, in relation to cholecystokinin. Eur J Pharmacol.?1992 Apr 29;215(1):23-8.
动态评分
0.0