| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
| Targets |
Human Endogenous Metabolite P2Y14 Receptor 0.67 μM (EC50)
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|---|---|
| ln Vitro |
UDP-galactose 2, UDP-glucuronic acid 3, and UDP-N-acetylglucosamine 4a also were agonists with potencies similar to that of UDP-glucose 1 at the P2Y14 receptor. The maximal effect observed with 2, 3, and 4a was somewhat variable. Maximal effects identical to that of UDP-glucose were observed in some experiments, whereas the maximal effects observed with these three molecules were somewhat less than that of UDP-glucose in other experiments. 2-Thio-UDP-glucuronic acid 28 acted as an agonist at the P2Y14 receptor and was equipotent to compounds 1 and 3. Thus, the favorable 2-thio modification preserved but did not enhance the potency of a hexose sugar-modified analogue. UDP-glucose (UDPG) and derivatives are naturally occurring agonists of the Gi protein-coupled P2Y14 receptor, which occurs in the immune system. We synthesized and characterized pharmacologically novel analogues of UDPG modified on the nucleobase, ribose, and glucose moieties, as the basis for designing novel ligands in conjunction with modeling. The recombinant human P2Y14 receptor expressed in COS-7 cells was coupled to phospholipase C through an engineered Galpha-q/i protein. Most modifications of the uracil or ribose moieties abolished activity; this is among the least permissive P2Y receptors. However, a 2-thiouracil modification in 15 (EC50 49 +/- 2 nM) enhanced the potency of UDPG (but not UDP-glucuronic acid) by 7-fold. 4-Thio analogue 13 was equipotent to UDPG, but S-alkylation was detrimental. Compound 15 was docked in a rhodposin-based receptor homology model, which correctly predicted potent agonism of UDP-fructose, UDP-mannose, and UDP-inositol. The hexose moiety of UDPG interacts with multiple H-bonding and charged residues and provides a fertile region for agonist modification [1].
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| Enzyme Assay |
Assay of P2Y14 receptor-stimulated PLC activity
COS-7 cells were transiently transfected with the human P2Y14 receptor and Gαqi5. Twenty-four hours after transfection, the inositol lipid pool of the cells was radiolabeled by incubation in 200 µL of serum-free inositol-free Dulbecco's modified Eagle's medium, containing 0.4 µCi of myo-[3H]inositol. No changes of medium were made subsequent to the addition of [3H]inositol. Forty-eight hours after transfection, cells were challenged with 50 µL of the five-fold concentrated solution of receptor agonists in 200 mM N-(2-hydroxyethyl)-piperazine-N′-2-ethanesulfonic acid, pH 7.3, containing 50 mM LiCl for 20 min at 37 °C. Incubations were terminated by aspiration of the drug-containing medium and addition of 450 µL of ice-cold 50 mM formic acid. After 15 min at 4 °C, samples were neutralized with 150 µL of 150 mM NH4OH. [3H]Inositol phosphates were isolated by ion exchange chromatography on Dowex AG 1-X8 columns as previously described [1]. |
| References |
[1]. Ko H, et al. Structure-activity relationship of uridine 5'-diphosphoglucose analogues as agonists of the human P2Y14 receptor. J Med Chem. 2007 May 3;50(9):2030-9.
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| Molecular Formula |
C15H24N2O17P2
|
|---|---|
| Molecular Weight |
566.30
|
| Exact Mass |
566.05502
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| CAS # |
2956-16-3
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| Related CAS # |
UDP-Galactose disodium;137868-52-1
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| Appearance |
Solid powder
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| Source |
Gut microbial metabolite
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| LogP |
-6.3
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| tPSA |
292Ų
|
| SMILES |
OC[C@@H]1O[C@H](OP(OP(OC[C@@H]2O[C@@H](N3C=CC(=O)NC3=O)[C@H](O)[C@H]2O)(O)=O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O
|
| InChi Key |
HSCJRCZFDFQWRP-ABVWGUQPSA-N
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| InChi Code |
InChI=1S/C15H24N2O17P2/c18-3-5-8(20)10(22)12(24)14(32-5)33-36(28,29)34-35(26,27)30-4-6-9(21)11(23)13(31-6)17-2-1-7(19)16-15(17)25/h1-2,5-6,8-14,18,20-24H,3-4H2,(H,26,27)(H,28,29)(H,16,19,25)/t5-,6-,8+,9-,10+,11-,12-,13-,14-/m1/s1
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| Chemical Name |
[[(2R,3S,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hydrogen 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7658 mL | 8.8292 mL | 17.6585 mL | |
| 5 mM | 0.3532 mL | 1.7658 mL | 3.5317 mL | |
| 10 mM | 0.1766 mL | 0.8829 mL | 1.7658 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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