| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
|
Purity: ≥98%
CE-224535 is a novel and selective P2X7 receptor antagonist that can be potentially used for the treatment of rheumatoid arthritis and osteoarthritis. Clinical trials showed that CE-224,535 was not efficacious as compared with placebo, for the treatment of RA in patients with an inadequate response to MTX. CE-224,535 demonstrated an acceptable safety and tolerability profile.
| ln Vitro |
CE-224535 is a selective antagonist of the human P2X7 receptor and was created as a disease-modifying antirheumatic medication (DMARD). Rheumatoid arthritis (RA) may now be treated with CE-224535, a novel therapy that can inhibit leukocytes' production of IL-1 and IL-18 [1].
|
|---|---|
| ln Vivo |
CE-224535 had a half-life of 2.4 hours in rats due to a lower CLp of 11 mL/min/kg and a greater Vdss of 7.6 L/kg. CE-224535 was given orally to rats at a dose of 5 mg/kg, and after that, the maximum plasma exposure (Cmax) was roughly 90 times more than its IC90 in human blood (Cmax=0.21 μg/mL or 0.44 μM). Although CE-224535's oral bioavailability in rats is low (F=2.6%), it is thought to be rat-specific because it is sufficient when it comes to oral bioavailability in dogs (59%) and monkeys (22%).
|
| References |
[1]. Stock TC, et al. Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol. 2012 Apr;39(4):720-7.
[2]. Duplantier AJ, et al. Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3708-11 |
| Molecular Formula |
C22H29N4O6CL
|
|---|---|
| Molecular Weight |
480.94186
|
| CAS # |
724424-43-5
|
| SMILES |
O=C(N1C[C@@H](O)COC)N(C2=CC=C(Cl)C(C(CCC3(O)CCCCCC3)=O)=C2)N=CC1=O
|
| InChi Key |
IRTORRLRMYAEAR-QGZVFWFLSA-N
|
| InChi Code |
InChI=1S/C23H30ClN3O6/c1-33-15-17(28)14-26-21(30)13-25-27(22(26)31)16-6-7-19(24)18(12-16)20(29)8-11-23(32)9-4-2-3-5-10-23/h6-7,12-13,17,28,32H,2-5,8-11,14-15H2,1H3/t17-/m1/s1
|
| Chemical Name |
2-(4-Chloro-3-(3-(1-hydroxycycloheptyl)propanoyl)phenyl)-4-((2R)-2-hydroxy-3-methoxy-propyl)-1,2,4-triazine-3,5-dione
|
| Synonyms |
CE-224,535; CE 224,535; CE224,535; CE-224535; CE 224535; CE224535;
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~100 mg/mL (~207.93 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 10 mg/mL (20.79 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 100.0 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: ≥ 10 mg/mL (20.79 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 100.0 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: ≥ 10 mg/mL (20.79 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 | 2.0793 mL | 10.3963 mL | 20.7926 mL | |
| 5 mM | 0.4159 mL | 2.0793 mL | 4.1585 mL | |
| 10 mM | 0.2079 mL | 1.0396 mL | 2.0793 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