| Targets |
The molecular target of Y1 receptor antagonist 1 formic is the neuropeptide Y1 receptor (NPY1R), a GPCR that is widely expressed in the central and peripheral nervous systems [14L6-L7, L11, L22-L23, L27, L30]. As an antagonist, it binds to the Y1 receptor and blocks the action of its endogenous ligands, neuropeptide Y (NPY) and peptide YY (PYY). By blocking Y1 signaling, the compound can inhibit vasoconstriction and regulate other NPY-mediated physiological processes.
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| ln Vitro |
As a Y1 receptor antagonist, this compound is expected to potently block Y1 receptor-mediated signaling in vitro. While specific potency data for the formic acid salt form is not detailed, the parent compound Y1 receptor antagonist 1 is a potent antagonist that inhibits NPY-induced calcium mobilization and other downstream signaling pathways in Y1-expressing cell lines. The formic acid salt formulation improves the aqueous solubility and handling properties of the active antagonist for research applications.
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| ln Vivo |
Y1 receptor antagonists are known to be active in vivo. By blocking the vasoconstrictor effects of NPY, Y1 antagonists can lower blood pressure and improve blood flow. They have been studied in animal models of hypertension, heart failure, and other cardiovascular diseases. The demonstration that this compound can be used for the study of cardiovascular diseases, such as vasoconstriction, suggests that it has appropriate PK properties to reach systemic circulation and block Y1 receptors in vivo [14L7-L8].
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| Enzyme Assay |
A radioligand binding assay is used to determine the affinity and selectivity of the antagonist for the Y1 receptor. Procedure: Membranes prepared from cells expressing recombinant human Y1 receptor are incubated with 0.1-1 nM of a radiolabeled Y1 receptor ligand (e.g., [125I]-PYY or [125I]-NPY) and varying concentrations of Y1 receptor antagonist 1 formic (e.g., 0.1 nM to 10 microM) in binding buffer for 60-90 minutes at 25degC. Bound radioligand is separated by rapid filtration through GF/B glass fiber filters. Radioactivity is measured with a scintillation counter. IC50 and Ki values are calculated from competitive binding curves.
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| Cell Assay |
Functional antagonism of the Y1 receptor can be measured using a calcium mobilization assay. Procedure: CHO-K1 or HEK-293 cells stably expressing the human Y1 receptor and a calcium-sensitive dye (e.g., Fluo-4-AM) are seeded in 384-well plates at 20,000 cells/well. Cells are washed and loaded with Fluo-4-AM dye in HBSS buffer for 60 minutes at 37degC. Y1 receptor antagonist 1 formic is added at varying concentrations (e.g., 0.1 nM to 10 microM) and incubated for 15 minutes. The Y1 agonist (e.g., NPY or PYY) is then added at the EC80 concentration, and the change in fluorescence (excitation 485 nm, emission 525 nm) is measured. The IC50 value is calculated as the concentration that inhibits 50% of the agonist-induced calcium flux.
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| Animal Protocol |
Y1 receptor antagonist can be tested in a rat model of NPY-induced vasoconstriction. Procedure: Male Sprague-Dawley rats are anesthetized, and the femoral artery is cannulated for blood pressure measurement. NPY (10 microg/kg) is administered intravenously to induce a robust and reproducible pressor (blood pressure increase) response. Y1 receptor antagonist 1 formic is administered intravenously or orally 15-30 minutes prior to NPY challenge at doses of 0.1-10 mg/kg. The percent inhibition of the NPY-induced pressor response is calculated. A dose-dependent inhibition confirms in vivo target engagement and functional antagonism of the Y1 receptor.
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| ADME/Pharmacokinetics |
Specific PK parameters are not provided for the Y1 receptor antagonist. As a small molecule antagonist, the parent compound is likely designed for good oral absorption and metabolic stability. The conversion to a formic acid salt (formate salt) is a common pharmaceutical formulation strategy to improve aqueous solubility, which can enhance dissolution and potentially bioavailability. The salt form can also improve the compound's physical and chemical stability during storage.
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| Toxicity/Toxicokinetics |
Specific toxicology data for Y1 receptor antagonist 1 formic is not available. As a receptor antagonist that modulates cardiovascular and possibly neuroendocrine function, the primary potential toxicities would likely be mechanism-based (on-target) effects. For a Y1 antagonist, these could include hypotension (low blood pressure), reflex tachycardia, and potentially changes in appetite or stress responses depending on the degree of CNS penetration. A comprehensive toxicology evaluation would be required.
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| References | |
| Additional Infomation |
Y1 receptor antagonist 1 formic (H 409-22 isomer formic) is a research chemical that serves as a formic acid salt of a Y1 receptor antagonist [14L9-L11, L21-L23]. Neuropeptide Y (NPY) is a widely distributed neurotransmitter that activates Y1, Y2, Y4, and Y5 receptors. Y1 receptors are prominently involved in vasoconstriction and vascular smooth muscle cell proliferation, making them a therapeutic target for cardiovascular diseases such as hypertension and restenosis after angioplasty [14L7-L8]. This antagonist also has potential applications in research related to obesity, feeding behavior, and stress [14L7-L8]. This product is for research use only and is not an approved therapeutic agent.
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| Appearance |
White to off-white solid powder
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| Synonyms |
409-22 isomer formic
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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: (1). 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 : ~125 mg/mL (~234.25 mM; with ultrasonication)
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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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