| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| 100mg |
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Purity: ≥98%
BIIE0246 (BIIE-0246) is a newly synthesized, potent and highly selective non-peptide neuropeptide Y (NPY) Y2 receptor antagonist with an IC50 of 15 nM. It was able to compete with high affinity (8 to 15 nM) for specific [(125)I]PYY(3 - 36) binding sites in HEK293 cells transfected with the rat Y(2) receptor cDNA, and in rat brain and human frontal cortex membrane homogenates. Interestingly, in rat brain homogenates while NPY, C2-NPY and PYY(3 - 36) inhibited all specific [(125)I]PYY(3 - 36) labelling, BIIE0246 failed to compete for all specific binding suggesting that [(125)I]PYY(3 - 36) recognized, in addition to the Y(2) subtype, another population of specific NPY binding sites, most likely the Y(5) receptor. Quantitative receptor autoradiographic data confirmed the presence of [(125)I]PYY(3 - 36)/BIIE0246-sensitive (Y(2)) and-insensitive (Y(5)) binding sites in the rat brain as well as in the marmoset monkey and human hippocampal formation. In the rat vas deferens and dog saphenous vein (two prototypical Y(2) bioassays), BIIE0246 induced parallel shifts to the right of NPY concentration-response curves with pA(2) values of 8.1 and 8.6, respectively. In the rat colon (a Y(2)/Y(4) bioassay), BIIE0246 (1 microM) completely blocked the contraction induced by PYY(3 - 36), but not that of [Leu(31), Pro(34)]NPY (a Y(1), Y(4) and Y(5) agonist) and hPP (a Y(4) and Y(5) agonist). Additionally, BIIE0246 failed to alter the contractile effects of NPY in prototypical Y(1) in vitro bioassays. Taken together, these results demonstrate that BIIE0246 is a highly potent, high affinity antagonist selective for the Y(2) receptor subtype. It should prove most useful to establish further the functional role of the Y(2) receptor in the organism. europeptide Y (NPY) plays an important role in the regulation of energy homeostasis in the level of central and sympathetic nervous systems (SNSs).
| ln Vitro |
In HEK 293 cells transfected with rat Y2 receptor cDNA, receptor binding tests demonstrated that BIIE-0246 competes for the particular [125I]PYY3-36 binding site with a high affinity (IC50=15±3 nM). On the other hand, in transfected HEK 293 cells, BIIE-0246 was not able to compete for the numerous specific [125I]GR231118, [125I]hPP, and [125I][Leu31, Pro34]PYY binding sites, even at concentrations up to 10 μM. They are cDNA for the rat Y1, Y4, or Y5 receptor [1].
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| ln Vivo |
Genetically fat NPY mice have higher body weights and levels of adiposity when fed a chow diet. In both genotypes, BIIE-0246 therapy led to weight growth after 4.5 and 2 weeks. On fat mass increase, BIIE-0246 had no discernible effect. Body weight and composition in DIO were affected by BIIE-0246 differently depending on genotype (treatment × genotype interaction, P < 0.05 for body weight, P < 0.001 for fat mass, and P < 0.05 for lean mass). Post hoc analyses revealed a trend toward lower gains in lean mass and higher gains in body weight and fat mass in the DIO-WT group. BIIE-0246 prevented DIO-NPY from experiencing an increase in fat mass (P=0.05). It's interesting to note that higher cholesterol levels were not seen in the 4.5-week cohort, but were present in WT mice given BIIE-0246 for two weeks. In both DIO-NPY treatment groups (P<0.01 for DIO-NPY vehicle; P<0.001 for DIO-NPY BIIE-0246), cholesterol levels were positively correlated with body fat mass; this relationship was not observed in any other group. Additionally, the regression curves for fat mass and cholesterol were significantly lower in the DIO-NPY group treated with BIIE-0246 than in the vehicle-treated group [2].
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| References |
[1]. Dumont Y, et al. BIIE0246, a potent and highly selective non-peptide neuropeptide Y Y(2) receptor antagonist. Br J Pharmacol. 2000 Mar;129(6):1075-88.
[2]. Liisa Ailanen, et al. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice. Front Pharmacol. 2018; 9: 319 |
| Molecular Formula |
C49H57N11O6
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|---|---|
| Molecular Weight |
896.046980000001
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| CAS # |
246146-55-4
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| Related CAS # |
BIIE-0246 hydrochloride
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| SMILES |
O=C(NCCN1C(N(C2=CC=CC=C2)N(C3=CC=CC=C3)C1=O)=O)[C@@H](NC(CC4(CC(N5CCN(C6C7=CC=CC=C7C(NC8=CC=CC=C68)=O)CC5)=O)CCCC4)=O)CCC/N=C(N)\N
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| InChi Key |
RSJAXPUYVJKAAA-JPGJPTAESA-N
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| InChi Code |
InChI=1S/C49H57N11O6/c50-46(51)53-25-13-22-40(45(64)52-26-27-58-47(65)59(34-14-3-1-4-15-34)60(48(58)66)35-16-5-2-6-17-35)54-41(61)32-49(23-11-12-24-49)33-42(62)56-28-30-57(31-29-56)43-36-18-7-8-19-37(36)44(63)55-39-21-10-9-20-38(39)43/h1-10,14-21,40,43H,11-13,22-33H2,(H,52,64)(H,54,61)(H,55,63)(H4,50,51,53)/t40-,43?/m0/s1
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| Chemical Name |
(2S)-5-(diaminomethylideneamino)-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-2-[[2-[1-[2-oxo-2-[4-(6-oxo-5,11-dihydrobenzo[c][1]benzazepin-11-yl)piperazin-1-yl]ethyl]cyclopentyl]acetyl]amino]pentanamide
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| Synonyms |
AR-H 053591; BIIE-0246; CHEMBL540989; GTPL1547; AR H 053591; BIIE-0246; AR-H-053591; AR H053591; ARH053591; BIIE 0246; CTK8E9439; BIIE0246;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~111.60 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1160 mL | 5.5800 mL | 11.1601 mL | |
| 5 mM | 0.2232 mL | 1.1160 mL | 2.2320 mL | |
| 10 mM | 0.1116 mL | 0.5580 mL | 1.1160 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 (A,D)Body weight,(B,E)fat mass and(C,F)lean mass gain in OE-NPYDβHand WT mice on chow (n= 11–12/group)(A–C)or Western diet (n= 7–11/group)(D–F)treated with Y2-receptor antagonist (BIIE0246) or vehicle for 4.5 or 2 weeks, respectively.Front Pharmacol.2018 Apr 5;9:319. |
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(A)Representative H&E stainings of liver slides with × 20 magnification (scale bar 100 μm), and(B)triglycerides and(C)cholesterol in the livers of mice on chow diet treated with Y2-receptor antagonist (BIIE0246) or vehicle for 4.5 weeks (n= 8–12/group).Front Pharmacol.2018 Apr 5;9:319. |
(A–D)mRNA expression ofNpy,(E–H)Th(I,J)Pomcand(K,L)Y2rin the hypothalamus and the brainstem of chow-(A,B,E,F,I,K)or Western-diet-fed(C,D,G,H,J,L)OE-NPYDβHand WT mice (n= 6–12/group) after 2-week Y2-receptor antagonist (BIIE0246) or vehicle |
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