P2Y14R antagonist 1 (compound I-17) is a potent and selective P2Y14R antagonist with an IC50 of 0.6 nM. P2Y14R antagonist 1 exhibits potent P2Y14R antagonist activity, as well as in vitro and in vivo efficacy and good pharmacokinetic properties. P2Y14R antagonist 1 reduces the release of inflammatory factors and cell pyroptosis through the NOD-like receptor family tumor virus protein (NLRP3)/ tumor virus protein D (GSDMD) signaling pathway. P2Y14R antagonist 1 is expected to be used in the research of acute gouty arthritis.

Physicochemical Properties

Molecular Formula	C15H12BRN3O2
Molecular Weight	346.18
CAS #	2728291-29-8
Appearance	Typically exists as solid at room temperature
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	P2Y14 Receptor 0.6 nM (IC50) P2Y2 Receptor > 100 nM (IC50) P2Y6 Receptor 89.7 nM (IC50) P2Y12 Receptor > 100 nM (IC50) P2Y1 Receptor > 100 nM (IC50) NLRP3
ln Vitro	P2Y14R antagonist 1 (compound I-17) (2-256 μM, 24 hours) at concentrations below 256 μM did not show significant cytotoxicity in RAW264.7 cells[1]. P2Y14R antagonist 1 (10-40 μM, 1 hour) can antagonize the effects of Uric acid sodium (HY-B2130A) and Lipopolysaccharides (HY-D1056) and has the property of inhibiting gout inflammation[1]. P2Y14R antagonist 1 (10-40 μM, 1 hour) acts upstream of NLRP3 inflammasome assembly and inhibits subsequent caspase-1 activation and macrophage pyroptosis[1].
ln Vivo	P2Y14R antagonist 1 (compound I-17) (5-20 mg/mL, intraperitoneal injection, injection time 1 hour) can promote the inflammation of acute gouty arthritis caused by Uric acid sodium (HY-B2130A) crystal injection in the Uric acid sodium (HY-B2130A)-induced mouse gout model [1].
Cell Assay	Cell Viability Assay[1] Cell Types: RAW264.7 Tested Concentrations: 2-256 μM Incubation Duration: 24 h Experimental Results: Only exhibited significant cytotoxicity only at a dose of 256 μM. Western Blot Analysis[1] Cell Types: RAW264.7 Tested Concentrations: 10-40 μM Incubation Duration: 1 h Experimental Results: Inhibited the expression of NLRP3 and GSDMD in MSU- and LPS-treated RAW264.7 cells. Immunofluorescence[1] Cell Types: RAW264.7 Tested Concentrations: 10-40 μM Incubation Duration: 1 h Experimental Results: Significantly reduced the formation of ASC specks induced by MSU and LPS.
Animal Protocol	Animal/Disease Models:Acute gouty arthritis model[1] Doses: 5-20 mg/mL Route of Administration: Intraperitoneal injection (i.p.) , Injection time: 60 min Experimental Results: Effectively reduced paw swelling in the MSU-induced mouse gout model, significantly decreased the production of pro-inflammatory cytokines IL-1β, IL-6, and IL-18 induced by MSU, markedly inhibited inflammatory cell infiltration in foot tissues induced by MSU, and significantly suppressed the increase of NLRP3 induced by MSU.
References	[1]. Discovery of N-Substituted Acetamide Derivatives as Promising P2Y14R Antagonists Using Molecular Hybridization Based on Crystallographic Overlay. J Med Chem. 2024 Jun 27;67(12):10233-10247.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8887 mL	14.4434 mL	28.8867 mL
	5 mM	0.5777 mL	2.8887 mL	5.7773 mL
	10 mM	0.2889 mL	1.4443 mL	2.8887 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.