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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
MDL-29951 is a potent glycine antagonist of NMDA (N-methyl-D-aspartate) receptor activation with Ki value of 0.14 μM in an in vitro and in vivo [3H]glycine binding assay. MDL 100,748 and MDL 29,951 are approximately 2000-fold selective for the glycine binding site relative to the glutamate recognition sites.The MDL29951-activated receptor exhibits other activities associated with GPCR-mediated signaling, including G protein-dependent activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and recruitment of β-arrestin. MDL29951 did not activate any of the known uracil or adenine nucleotide-activated P2Y receptors or cysteinyl leukotriene receptors. Gαi- and Gαq-dependent signaling responses also were observed in primary rat oligodendrocytes in the presence of MDL29951. Moreover, MDL29951 diminished myelination in primary oligodendrocytes isolated from heterozygous mice but had no effect on myelination in oligodendrocytes from GPR17 knockout mice. Effects of a small-molecule GPR17 agonist observed during oligodendrocyte differentiation support the idea that development of antagonists of GPR17 is a rational goal for elaboration of pharmacotherapies in demyelinating diseases.
ln Vitro |
The glycine binding site is about 2000 times more selective than the glutamate recognition site for MDL 100,748 and MDL 29,951 [1]. MDL-29951 has an IC50 value of 2.5 μM, which inhibits human F16Bpase. MDL-29951 is less effective against the rat liver isoform (IC50=11 μM) but inhibits the enzyme isoforms of the human liver (IC50=2.5 μM), pig kidney (IC50=1.0 μM), and rabbit liver (IC50=0.21 μM)[2]. In addition to these GPCR-mediated signaling functions, MDL29951-activated receptors also recruit beta-arrestin and activate extracellular signal-regulated kinases 1 and 2 (ERK1/2) in a G protein-dependent manner. Similar to the recombinant cell system, MDL29951 stimulates rat oligodendrocyte precursor cells to accumulate cyclic adenosine monophosphate (cAMP) and inhibit Ca2+ signaling responses during the peak of GPR17 abundance. In cells with low GPR17 abundance, MDL29951's effect was significantly reduced, and pranlukast blocked it [3].
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ln Vivo |
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Animal Protocol |
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References |
[1]. Baron BM, et al. Potent indole- and quinoline-containing N-methyl-D-aspartate antagonists acting at the strychnine-insensitive glycine binding site. J Pharmacol Exp Ther. 1992 Sep;262(3):947-56.
[2]. Wright SW, et al. 3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site. Bioorg Med Chem Lett. 2003 Jun 16;13(12):2055-8. [3]. Harden TK. Enigmatic GPCR finds a stimulating drug. Sci Signal. 2013 Oct 22;6(298):pe34 |
Molecular Formula |
C12H9CL2NO4
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Molecular Weight |
302.11
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CAS # |
130798-51-5
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Related CAS # |
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
O=C(O)CCC1=C(C(O)=O)NC2=C1C(Cl)=CC(Cl)=C2
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Synonyms |
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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 |
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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) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.28 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.28 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.3101 mL | 16.5503 mL | 33.1005 mL | |
5 mM | 0.6620 mL | 3.3101 mL | 6.6201 mL | |
10 mM | 0.3310 mL | 1.6550 mL | 3.3101 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.