BIBP3226
目录号 : GC48494
A nonpeptide antagonist of NPY receptor Y1
Cas No.:159013-54-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
BIBP3226 is a nonpeptide antagonist of neuropeptide Y (NPY) receptor Y1 (Ki = 1.1 nM).1 It is selective for Y1 over Y2, Y4, and Y5 receptors (Kis = >1,000 nM for all). It also binds to neuropeptide FF receptor 1 (NPFF1) and NPFF2 (Kis = 108 and 79 nM, respectively) and reverses NPFF-induced inhibition of forskolin-induced cAMP accumulation in CHO cells expressing human NPFF2 in a concentration-dependent manner.1 BIBP3226 inhibits NPY-induced increases in perfusion pressure in isolated rat kidney but not the NPY-induced twitch response in isolated rat vas deferens (IC50s = 26 and >10,000 nM, respectively).2 BIBP3226 inhibits NPY-induced increases in blood pressure in pithed rats (ED50 = 0.11 mg/kg).2 It also inhibits NPFF-induced hypothermia in mice when administered intracerebroventricularly (i.c.v.) at a dose of 5 nmol.3
1.Mollereau, C., GouardÈres, C., Dumont, Y., et al.Agonist and antagonist activities on human NPFF2 receptors of the NPY ligands GR231118 and BIBP3226Br. J. Pharmacol.133(1)1-4(2001) 2.Rudolf, K., Eberlein, W., Engel, W., et al.The first highly potent and selective non-peptide neuropeptide Y Y1 receptor antagonist: BIBP3226Eur. J. Pharmacol.271(2-3)R11-R13(1994) 3.Fang, Q., Guo, J., He, F., et al.In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonistPeptides27(9)2207-2213(2006)
| Cas No. | 159013-54-4 | SDF | |
| Canonical SMILES | OC(C=C1)=CC=C1CNC([C@@H](CCCNC(N)=N)NC(C(C2=CC=CC=C2)C3=CC=CC=C3)=O)=O | ||
| 分子式 | C27H31N5O3 | 分子量 | 473.6 |
| 溶解度 | DMSO: soluble,Ethanol: soluble | 储存条件 | -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1115 mL | 10.5574 mL | 21.1149 mL |
| 5 mM | 0.4223 mL | 2.1115 mL | 4.223 mL |
| 10 mM | 0.2111 mL | 1.0557 mL | 2.1115 mL |
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Apparent affinity and potency of BIBP3226, a non-peptide neuropeptide Y receptor antagonist, on purported neuropeptide Y Y1, Y2 and Y3 receptors
Eur J Pharmacol 1995 May 4;278(1):R3-5.PMID:7664808DOI:10.1016/0014-2999(95)00179-o.
The newly developed, purported non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 was evaluated for its potential effect on the recently characterized Y3 receptor subtype and for its apparent affinity in rat and human brain membrane binding assays using highly selective neuropeptide Y Y1 and Y2 radioligands. BIBP3226 potently blocked (pA2 = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y1 receptor bioassay and demonstrated nM affinity for Y1/[125I][Leu31,Pro34]peptide YY binding sites. In contrast, it failed to antagonize the biological effects of neuropeptide Y in the rat vas deferens (Y2) and rat colon (Y3) and did not significantly competed for Y2/[125I]peptide YY-(3-36) binding sites in rat and human brain homogenates. Taken together, the results demonstrate further the high potency and selectivity of BIBP3226 for the neuropeptide Y Y1 receptor by establishing its lack of antagonist activity on the Y3 subtype.
BIBP3226 inhibits neuropeptide Y and pancreatic polypeptide potentiated neurogenic vasoconstriction
Life Sci 1998;62(6):525-32.PMID:9464464DOI:10.1016/s0024-3205(97)01148-x.
Neuropeptide Y (NPY) potentiates the contractile response of the rat caudal artery to adrenergic nerve stimulation in-vitro. The NPY Y1 selective antagonist BIBP3226 ((R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-argininami de), inhibited the vascular effects of NPY in rat caudal artery preparations in-vitro (IC50 =126 nM). BIBP3226 also inhibited the effects of the selective Y1 agonist [Leu31,Pro34]NPY and completely abolished the effects of avian pancreatic polypeptide that was shown to be capable of potentiating neurogenic vasoconstriction in this preparation. These effects were reversible and are most likely mediated by the Y1 receptor subtype since we failed to observe any functional evidence of a Y2 receptor subtype in rat caudal artery. The caudal artery provides a useful functional assay for pharmacological analysis of NPY and NPY antagonists.
Non-competitive binding of the nonpeptide antagonist BIBP3226 to rat forebrain neuropeptide Y1 receptors
Eur J Pharmacol 1997 Jul 23;331(2-3):275-84.PMID:9274990DOI:10.1016/s0014-2999(97)01016-9.
[3H]Neuropeptide Y labelled neuropeptide Y receptors in rat forebrain membranes as a homogenous class of high-affinity sites. Between 80 and 85% of these receptors showed high affinity for Y1-selective antagonists such as (R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine amide (BIBP3226). While competitive in functional studies, BIBP3226 produced parallel shifts of the Scatchard plots of [3H]neuropeptide Y saturation binding in rat forebrain membranes. Mechanisms which are routinely invoked to explain non-competitive binding do not apply to BIBP3226. Wash-out experiments, involving successive treatment of the membranes with BIBP3226, buffer (wash-out step) and [3H]neuropeptide Y, argue against irreversible or a pseudo-irreversible binding of the antagonist. Allosteric inhibition is also unlikely since BIBP3226 did not affect the rate of dissociation of [3H]neuropeptide Y in isotope dilution experiments. The non-hydrolyzable guanine nucleotide, 5'-guanylylimidodiphosphate (Gpp(NH)p), abolished the binding of [3H]neuropeptide Y and increased its rate of dissociation in isotope dilution experiments. This suggests that the initial [3H]neuropeptide Y-receptor association is a low affinity process and that the observed binding of [3H]neuropeptide Y is related to the formation of a ternary [3H]neuropeptide Y-receptor-G protein complex. Two- or even multistate models (in which BIBP3226 could potentially behave as an inverse agonist) could therefore be needed to explain the non-competitive antagonism of BIBP3226 in broken cell preparations.
In vivo inhibition of neuropeptide FF agonism by BIBP3226, an NPY Y1 receptor antagonist
Peptides 2006 Sep;27(9):2207-13.PMID:16762456DOI:10.1016/j.peptides.2006.04.002.
BIBP3226 {(R)-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)-methyl]-argininamide} was recently shown to display relatively high affinities for neuropeptide FF (NPFF) receptors and exhibit antagonist activities towards NPFF receptors in vitro. The present study was undertaken to investigate the antagonistic effects of BIBP3226 on several in vivo pharmacologic profiles induced by exogenous NPFF and NPVF. (1) BIBP3226 (5 nmol) injected into the third ventricle completely antagonized the hypothermic effects of NPFF (30 nmol) and NPVF (30 nmol) after cerebral administration in mice; (2) BIBP3226 (5 nmol, i.c.v.) prevented the anti-morphine actions of NPFF (10 nmol, i.c.v.) in the mouse tail-flick assay; (3) in urethane-anaesthetized rats, both NPFF (200 nmol/kg, i.v.) and NPVF (200 nmol/kg, i.v.) increased the mean arterial blood pressure, which were significantly reduced by pretreatment with BIBP3226 (500 nmol/kg, i.v.). Collectively, these data suggest that BIBP3226, a mixed antagonist of NPY Y1 and NPFF receptors, shows in vivo antagonistic effects on NPFF receptors. In addition, it seems to be clear that the in vivo pharmacological profiles of NPFF are mediated directly by NPFF receptors.
Evidence for involvement of neuropeptide Y receptors in the regulation of food intake: studies with Y1-selective antagonist BIBP3226
Br J Pharmacol 1998 Aug;124(7):1507-15.PMID:9723965DOI:10.1038/sj.bjp.0701969.
1. Experiments were conducted to evaluate the effects of the novel non-peptide neuropeptide Y Y1 receptor antagonist, BIBP3226 (N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]-D-arginine amide) on spontaneous, fasting-induced and NPY-induced food intake in rats. In addition to consumption of regular chow, the effects of BIBP3226 on consumption of highly palatable sweetened mash were monitored in a 1 h test on first exposure and after familiarization with novel food. 2. BIBP3226 (10.0 nmol, i.c.v.) had no effect on the consumption of regular chow, but reduced significantly the intake of highly palatable diet and the food intake stimulated by fasting (24 h). Neuropeptide Y (NPY, 1.0 nmol, i.c.v.) significantly increased the consumption of regular rat chow. This orexigenic effect of NPY was blocked by BIBP3226 (10.0 nmol, administered i.c.v. 5 min before NPY) at 30 min and 4 h, but not at 1 and 2 h. When animals were pretreated with diazepam (0.5 mg kg(-1), i.p., 20 min before NPY), BIBP3226 failed to suppress NPY-induced feeding. 3. An NPY Y1 and Y3 receptor agonist, [Leu31,Pro34]NPY and a Y5 receptor agonist human peptide YY3-36 (hPYY3-36, both 30 pmol), microinjected into the paraventricular nucleus of the hypothalamus (PVN) increased the consumption of regular rat chow. BIBP3226 (0.4 nmol, into the PVN) completely blocked the stimulatory effect of [Leu31,Pro34]NPY but not that of hPYY3-36. BIBP3226 (0.4 nmol) alone failed to modify the consumption of the regular chow. Higher doses of BIBP3226 (1.0 and 2.0 nmol) injected into the vicinity of the PVN reduced the consumption of the sweetened mash. 4. These results suggest that both the NPY Y1 and Y5 receptors in the PVN are involved in the regulation of food intake. The stimulatory effect of exogenous NPY is probably mediated through an NPY receptor subtype that is not identical with the Y1 receptor (possibly Y5 receptor). However, the NPY Y1 receptors may mediate the effect of endogenous NPY in conditions of increased energy demand or on intake of highly palatable diets.