| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
P2Y14 receptor
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|---|---|
| ln Vitro |
UDP-glucose (UDPG), a glycosyl donor in the biosynthesis of carbohydrates, is an endogenous agonist of the G protein-coupled P2Y(14) receptor. RBL-2H3 mast cells endogenously express a P2Y(14) receptor at which UDPG mediates degranulation as indicated by beta-hexosaminidase (HEX) release. Both UDPG and a more potent, selective 2-thio-modified UDPG analog, MRS2690 (diphosphoric acid 1-alpha-d-glucopyranosyl ester 2-[(2-thio)uridin-5''-yl] ester), caused a substantial calcium transient in RBL-2H3 cells, which was blocked by pertussis toxin, indicating the presence of the G(i)-coupled P2Y(14) receptor, supported also by quantitative detection of abundant mRNA. Expression of the closely related P2Y(6) receptor was over 100 times lower than the P2Y(14) receptor, and the P2Y(6) agonist 3-phenacyl-UDP was inactive in RBL-2H3 cells. P2Y(14) receptor agonists also induced [(35)S]GTPgammaS binding to RBL-2H3 cell membranes, and phosphorylation of ERK1/2, P38 and JNK. UDPG and MRS2690 concentration-dependently enhanced HEX release with EC(50) values of 1150+/-320 and 103+/-18nM, respectively. The enhancement was completely blocked by pertussis toxin and significantly diminished by P2Y(14) receptor-specific siRNA. Thus, mast cells express an endogenous P2Y(14) receptor, which mediates G(i)-dependent degranulation and is therefore a potential novel therapeutic target for allergic conditions [1].
|
| References |
[1]. Biochem Pharmacol. 2010 Mar 15;79(6):873-9.
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| Additional Infomation |
Mast cell degranulation is associated with a variety of diseases, such as asthma and urticaria. We investigated the potential role of the P2Y(14) receptor (P2Y(14)R) and other P2Y isoforms in human LAD2 mast cell degranulation. All eight P2Y receptors were expressed in LAD2 cells, but at varying levels (quantitative real-time RT-PCR). The gene expression levels of ADP receptor, P2Y(1)R, P2Y(12)R, and P2Y(13)R were similar, while the expression levels of P2Y(11)R and P2Y(4)R were higher, at 5.8-fold and 3.8-fold, respectively, higher than that of P2Y(1)R. The expression level of P2Y(2)R was the lowest, 40-fold lower than that of P2Y(1)R, while the expression levels of P2Y(6)R and P2Y(14)R were ≤50% of that of P2Y(1)R. Individual natural P2YR agonists failed to induce β-hexosamine release, but certain nucleotides significantly enhanced C3a- or antigen-induced β-Hex release, with the potency order being ATP > UDPG ≥ ADP >> UDP, UTP. Despite high expression of P2Y(11)R and P2Y(4)R, they did not appear to play a major role in degranulation, as the P2Y(4)R agonist UTP and the P2Y(11)R agonists ATPγS and NF546 showed no significant effect. The selective P2Y(1)R agonist MRS2365 enhanced degranulation, but its potency was approximately 1000 times weaker than that of P2Y(1)R agonists, while the effect of the P2Y(6)R agonist 3-phenylacetyl-UDP was negligible. The enhancing effects of ADP and ATP appeared to be mediated through multiple receptors. The synthetic agonist MRS2690 of UDPG and P2Y(14)R both enhanced C3a-induced β-hexosamine release, while P2Y(14)R antagonists, specific P2Y(14)R siRNA, and pertussis toxin inhibited this release, suggesting that P2Y(14)R activation plays a role in promoting degranulation of human mast cells. Purinergic signaling. March 2013; 9(1):31-40.
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| Molecular Formula |
C15H24N2O16P2S
|
|---|---|
| Molecular Weight |
582.367385864258
|
| Exact Mass |
582.032
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| Elemental Analysis |
C, 28.77; H, 3.54; N, 4.47; Na, 7.34; O, 40.87; P, 9.89; S, 5.12
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| CAS # |
7077-89-6
|
| Related CAS # |
15039-58-4
|
| PubChem CID |
44422870
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| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.97±0.1 g/cm3(Predicted)
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| LogP |
-6
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| Hydrogen Bond Donor Count |
9
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
36
|
| Complexity |
970
|
| Defined Atom Stereocenter Count |
9
|
| SMILES |
S=C1NC(C=CN1[C@H]1[C@@H]([C@@H]([C@@H](COP(=O)(O)OP(=O)(O)O[C@@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)O1)O)O)=O
|
| InChi Key |
FWVUCDCDTDREPN-JZMIEXBBSA-N
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| InChi Code |
InChI=1S/C15H24N2O16P2S/c18-3-5-8(20)10(22)12(24)14(31-5)32-35(27,28)33-34(25,26)29-4-6-9(21)11(23)13(30-6)17-2-1-7(19)16-15(17)36/h1-2,5-6,8-14,18,20-24H,3-4H2,(H,25,26)(H,27,28)(H,16,19,36)/t5-,6-,8-,9-,10+,11-,12-,13-,14-/m1/s1
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| Chemical Name |
[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen phosphate
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| Synonyms |
MRS2690; 15039-58-4; AKOS024457332; Q27087781; disodium;[[(2R,3S,4R,5R)-3,4-dihydroxy-5-(4-oxo-2-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methoxy-oxidophosphoryl] [(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate
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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 |
| 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) |
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
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7171 mL | 8.5856 mL | 17.1712 mL | |
| 5 mM | 0.3434 mL | 1.7171 mL | 3.4342 mL | |
| 10 mM | 0.1717 mL | 0.8586 mL | 1.7171 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.
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