| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
IC50: 0.3 nM
DP receptor (Prostaglandin D2 receptor, DP1) [1]. |
|---|---|
| ln Vitro |
Prostaglandin D2 (PGD2) is a significant inflammatory mediator linked to allergic rhinitis and asthma. It is mostly produced when mast cells degranulate in response to an allergen, serving as the main cyclooxygenase metabolite. It has been demonstrated that blocking PGD2 with DP antagonists effectively reduces allergic rhinitis symptoms in a variety of species and, more precisely, prevents antigen-induced nasal congestion[2].
The functional antagonism of the aminopyrimidine compounds was determined by their ability to inhibit PGD2-induced cAMP accumulation in human LS174T cells, which endogenously express the human DP receptor. The potency is expressed as pIC50 (-log IC50) values, which range from approximately 6 to 10 for the compounds in the training set [1]. The CoMSIA (Comparative Molecular Similarity Indices Analysis) model developed from 40 training compounds revealed key pharmacophore features for DP antagonism: (1) Two hydrogen bond acceptors with a spatial separation of about 8 Å. One of these acceptors is preferably negatively charged, hypothesized to interact with Arg-310 in the 7th transmembrane domain. (2) A hydrogen bond donor adjacent to the main hydrophobic center. (3) A large hydrophobic center separating the two acceptors [1]. An external validation set of 20 compounds was used to test the predictive power of the model. The predicted pIC50 values from the three-component CoMSIA model correlated well with the experimental values, with a Q² of 0.70 and an R² of 0.91 [1]. |
| Cell Assay |
LS174T cells, which endogenously express the human DP receptor, were used for PGD2-induced cAMP assays. Cells were plated at 40,000 cells per well in a 96-well plate. After overnight incubation at 37°C, the medium was replaced. For IC50 determination of the antagonist compounds, they were pre-incubated with the cells for 15 minutes. Subsequently, the cells were stimulated with 15 nM of PGD2 for 15 minutes. cAMP accumulation in the stimulated cells was measured using a cAMP SPA (scintillation proximity assay) Direct Screening Assay System, following the procedures specified by the manufacturer [1].
|
| References | |
| Additional Infomation |
Prostaglandin D2 (PGD2) is a major inflammatory mediator implicated in asthma and allergic rhinitis. It exerts its actions by activating two G-protein-coupled receptors: DP (DP1) and CRTH2 (DP2). Blocking PGD2 using DP antagonists has been shown to be effective at alleviating the symptoms of allergic rhinitis in multiple species and inhibiting antigen-induced nasal congestion. DP antagonists are also reported to be effective in suppressing nicotinic acid-induced flushing [1].
The CoMSIA study was conducted on a structurally diverse series of 2,6-substituted-4-monosubstituted aminopyrimidines. The pharmacophore features defined by the model are consistent with various known DP receptor antagonists and are in good agreement with binding hypotheses derived from DP structural models and mutation studies [1]. |
| Molecular Formula |
C23H23CL2N3O3
|
|---|---|
| Molecular Weight |
460.3530
|
| Exact Mass |
459.111
|
| Elemental Analysis |
C, 60.01; H, 5.04; Cl, 15.40; N, 9.13; O, 10.43
|
| CAS # |
885066-67-1
|
| PubChem CID |
11669780
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
682.1±65.0 °C at 760 mmHg
|
| Flash Point |
366.3±34.3 °C
|
| Vapour Pressure |
0.0±2.2 mmHg at 25°C
|
| Index of Refraction |
1.622
|
| LogP |
6.28
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
31
|
| Complexity |
594
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C(C(C)(C)C1C=C(C2C=C(NCCC3C(Cl)=CC(Cl)=CC=3)N=C(OC)N=2)C=CC=1)O
|
| InChi Key |
FJKKCRCBBAXLQZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H23Cl2N3O3/c1-23(2,21(29)30)16-6-4-5-15(11-16)19-13-20(28-22(27-19)31-3)26-10-9-14-7-8-17(24)12-18(14)25/h4-8,11-13H,9-10H2,1-3H3,(H,29,30)(H,26,27,28)
|
| Chemical Name |
2-[3-[6-[2-(2,4-dichlorophenyl)ethylamino]-2-methoxypyrimidin-4-yl]phenyl]-2-methylpropanoic acid
|
| Synonyms |
MDK 66671; MDK66671; MDK-66671; PGD2-IN-1
|
| 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)
|
| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~54.31 mM)
|
|---|---|
| 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 | 2.1723 mL | 10.8613 mL | 21.7226 mL | |
| 5 mM | 0.4345 mL | 2.1723 mL | 4.3445 mL | |
| 10 mM | 0.2172 mL | 1.0861 mL | 2.1723 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA