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| 1mg |
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| Other Sizes |
| Targets |
BIIE-0246 hydrochloride targets the neuropeptide Y (NPY) Y2 receptor, which is a G protein-coupled receptor (GPCR) involved in numerous biological functions including appetite regulation, anxiety, memory, pain perception, and seizure activity. The Y2 receptor is predominantly presynaptic and functions as an inhibitory autoreceptor that regulates NPY release. It also plays a role in mediating NPY-induced vasoconstriction and angiogenesis. The compound is a highly selective and competitive non-peptide antagonist at this receptor.
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| ln Vitro |
In mouse podocytes induced by NPY (10, 100 ng/mL), BIIE-0246 hydrochloride (1 µM; 24 h) decreases the expression of p-AKT S473 and P-p44/42 MAPK [3].
In vitro, BIIE-0246 acts as a potent and selective antagonist of the NPY Y2 receptor with an IC50 of 15 nM. Functional assays typically measure its ability to block Y2 receptor-mediated responses, such as inhibition of cAMP accumulation or calcium mobilization. The compound displays no significant activity at Y1, Y4, and Y5 receptors up to concentrations of 10 microM, demonstrating its high selectivity. These properties make it a valuable tool for discerning Y2-specific effects. |
| ln Vivo |
While BIIE-0246 hydrochloride (1.3 mg/kg; Ip; daily for 2 or 4.5 weeks) causes a rise in obesity in WT mice, it protects diet-induced obesity in OE-NPYDβH mice [1]. In individuals with ADR nephropathy, BIIE-0246 hydrochloride (10 µg/day; ip; daily for 14 days) lowers albuminuria [3].
In vivo, BIIE-0246 has been extensively characterized in animal models of pain and itch. Studies have shown that in chronic pain models of latent sensitization, BIIE0246 produces a profound reinstatement of pain-like behaviors. These results indicate that Y2 receptors may have a protective role in certain chronic pain states. The compound is administered via various routes including intrathecal, intracerebroventricular, or systemic injection in rodent models to explore Y2 receptor function. |
| Enzyme Assay |
Binding assays for BIIE-0246 are typically performed using radioligand binding techniques on membrane preparations from cells expressing recombinant human NPY Y2 receptors or from rat brain hippocampal membranes. Various concentrations of the compound are incubated with a specific Y2 receptor radioligand such as [125I]PYY3-36 or [125I]NPY. After incubation, bound and free radioactivity are separated by filtration, and IC50 or Ki values are calculated from competition binding curves.
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| Cell Assay |
Western Blot Analysis[3]
Cell Types: Mouse podocytes Tested Concentrations: 1 µM Incubation Duration: 24 h Experimental Results: Blocked the NPY-stimulated phosphorylation of Akt and p44/42 MAPK. For in vitro functional assays, cells expressing NPY Y2 receptors (e.g., SK-N-BE neuroblastoma cells or transfected HEK293 cells) are used. Cells are pre-incubated with various concentrations of BIIE-0246, then stimulated with a Y2 receptor agonist such as NPY, PYY, or NPY13-36. Functional endpoints include measurement of inhibition of cAMP accumulation (using a FRET-based cAMP assay), intracellular calcium release, or beta-arrestin recruitment (using BRET-based assays). The ability of BIIE-0246 to block agonist-induced responses is measured. |
| Animal Protocol |
Animal/Disease Models: Homozygous transgenic male OE-NPYDβH and WT C57Bl/6N mice[1]
Doses: 1.3 mg/kg Route of Administration: Ip; daily for 2 or 4.5 weeks Experimental Results: Increased body weight gain in both genotypes on the chow diet caused metabolic disturbances , especially in WT mice. During energy surplus (ie, on Western diet), blocking of Y2-receptors induced obesity in WT mice and OE-NPYDβH mice demonstrated a decreased fat mass gain, hepatic glycogen and serum cholesterol levels relative to body adiposity. Animal/Disease Models: Male balb/c (Bagg ALBino) mouse[3] Doses: 10 µg/day Route of Administration: Ip; daily for 14 days Experimental Results: Reduces albuminuria in ADR nephropathy. In vivo animal studies using BIIE-0246 are typically conducted in rodent models of pain, itch, or feeding behavior. Common administration routes include intrathecal injection (for spinal effects), intracerebroventricular injection (for central effects), intraperitoneal, or subcutaneous injection. Doses vary depending on the route and model but typically range from 0.1 to 10 mg/kg. Endpoints include measurement of nociceptive thresholds (e.g., paw withdrawal latency in hot plate or tail-flick tests), itch behavior (scratching bouts), or food intake. Appropriate control groups (vehicle, Y2 agonist) are included. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for BIIE-0246 dihydrochloride are not extensively detailed in standard product literature. The compound has been shown to be active in vivo following systemic administration, indicating adequate absorption and distribution. Specific PK parameters such as bioavailability, half-life, clearance, and volume of distribution would need to be determined from dedicated studies. As a non-peptide small molecule (molecular weight approximately 969), it may have favorable drug-like properties.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for BIIE-0246 dihydrochloride are not extensively reported in available literature. The compound has been used in numerous in vivo studies without reports of overt toxicity at the doses employed. Standard preclinical safety assessments including acute and repeated-dose toxicity, genotoxicity, and safety pharmacology are not described in product documentation. For research use, standard chemical safety precautions should be followed.
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| References |
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| Additional Infomation |
BIIE-0246 dihydrochloride (AR-H 053591 dihydrochloride) has the molecular formula C49H50Cl2N11O6 and a molecular weight of 968.97. The CAS number for the dihydrochloride salt is 246146-31-6. It is a potent, selective, and competitive non-peptide antagonist of the neuropeptide Y Y2 receptor. The compound is used exclusively for research purposes to study NPY Y2 receptor biology. It is not approved for human therapy.
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| Molecular Formula |
C49H57N11O6.XHCL
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| Related CAS # |
BIIE-0246;246146-55-4
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 :~40 mg/mL
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
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.
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