| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
| Targets |
Polmacoxib targets cyclooxygenase-2 (COX-2) and carbonic anhydrase subtypes I (CAI) and CAII. COX-2 is the enzyme responsible for the production of prostaglandins that cause inflammation and pain. Carbonic anhydrases are zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. Inhibition of COX-2 reduces prostaglandin synthesis, while carbonic anhydrase inhibition may contribute to additional therapeutic effects.
|
|---|---|
| ln Vitro |
At a lower dose than Celecoxib, Polmacoxib (CG100649) (0-1 μg/ml; 24 hours; HCA-7 and HT-29 cells) can reduce PGE2 synthesis and COX-2 activity in human colon cancer cells[2].
Polmacoxib demonstrates potent inhibition of COX-2 with an IC50 value of 40 nM in the absence of carbonic anhydrase II. It also inhibits carbonic anhydrase subtypes I and CAII. Its dual inhibition profile distinguishes it from other NSAIDs. In vitro activity has been characterized in enzyme inhibition assays. The compound's selectivity for COX-2 over COX-1 and its carbonic anhydrase inhibition potency are key parameters. |
| ln Vivo |
In ApcMin/+ mice, polmacoxib (7 mg/kg; oral; once daily for 8 weeks) prevents the formation of intestinal polyps [2]. Tumor weight and volume were reduced by 58% and 48%, respectively, with polmacoxib (7–15 mg/kg); oral; once daily on days 27 to 111 postinjection; athymic nude mice; subcutaneous xenograft mouse model). % and 36%, respectively, following celecoxib therapy [2]. Orthotopic xenograft mouse models treated with polmacoxib (7–15 mg/kg; oral; starting on day 14 and continuing for 8 weeks; athymic nu/nu mice); this inhibits the growth of colorectal cancer (CRC) in these models. Tumor weight was reduced by 70% with 7 mg/kg or 83% with 15 mg/kg, in contrast to a 70% reduction following treatment with 500 mg/kg celecoxib [2].
Polmacoxib has been studied in clinical trials for the treatment of osteoarthritis. As an NSAID, it reduces pain and inflammation in patients with osteoarthritis. Its dual COX-2 and carbonic anhydrase inhibition may offer advantages in safety and efficacy. The compound's in vivo efficacy has been demonstrated in clinical studies. It is a drug candidate that has been evaluated for osteoarthritis of the hip and knee. |
| Enzyme Assay |
COX-2 enzyme inhibition assays are performed using recombinant human COX-2 enzyme. The enzyme is incubated with the substrate arachidonic acid and a peroxidase co-substrate in assay buffer. The reaction product prostaglandin G2 is detected by measuring the oxidation of a chromogenic co-substrate (e.g., TMPD) at 590 nm. Test compounds are serially diluted and added to the reaction mixture. IC50 values are determined by non-linear regression analysis. Each concentration is tested in duplicate. Carbonic anhydrase inhibition assays are performed using a stopped-flow CO2 hydration assay or an esterase activity assay.
|
| Cell Assay |
Cellular COX-2 inhibition is evaluated in cell lines stimulated to express COX-2 (e.g., macrophages stimulated with LPS). Cells are cultured in appropriate media at 37°C with 5% CO2 and treated with Polmacoxib at various concentrations (0.01-10 μM). Prostaglandin E2 (PGE2) levels in the culture supernatant are measured by ELISA. Cell viability is assessed using MTT or LDH assays. Each experiment includes known COX-2 inhibitors (e.g., celecoxib) as positive controls and vehicle controls.
|
| Animal Protocol |
In vivo efficacy is evaluated in animal models of inflammation and pain, such as the carrageenan-induced paw edema model and the adjuvant-induced arthritis model in rats. Polmacoxib is administered orally at doses typically ranging from 0.1-10 mg/kg. Paw swelling is measured by plethysmometry. Pain responses are assessed by the paw pressure test or hot plate test. Clinical studies have been conducted in patients with osteoarthritis of the hip and knee.
|
| ADME/Pharmacokinetics |
Polmacoxib has a molecular weight of 361.4 g/mol and a molecular formula of C18H16FNO4S. Purity: typically ≥95%. Storage: long-term storage in a cool, dry place. As a drug candidate, its pharmacokinetic parameters have been characterized in clinical studies. It is orally absorbed, metabolized in the liver, and excreted renally. Bioavailability and half-life data are available from clinical trials.
|
| Toxicity/Toxicokinetics |
Polmacoxib has been evaluated in clinical trials for safety and efficacy in osteoarthritis. It is generally well-tolerated at therapeutic doses. Common adverse effects may include gastrointestinal disturbances, headache, and dizziness. As a COX-2 inhibitor, it may have cardiovascular risks similar to other COX-2 inhibitors. Standard toxicology studies have demonstrated an acceptable safety profile. It is an NSAID drug candidate that has undergone clinical development.
|
| References |
|
| Additional Infomation |
Polmacoxib has been used in trials to investigate the treatment of osteoarthritis, hip osteoarthritis, knee osteoarthritis, localized primary osteoarthritis of the hip, and localized primary osteoarthritis of the knee.
Polmacoxib is also known as CG100649 and Acelex. Its chemical name is 4-[3-(3-Fluorophenyl)-4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl]benzenesulfonamide. It is a dual inhibitor of COX-2 and carbonic anhydrase. It has been studied in clinical trials for osteoarthritis. It has not received regulatory approval in all jurisdictions. |
| Molecular Formula |
C18H16FNO4S
|
|---|---|
| Molecular Weight |
361.38734
|
| Exact Mass |
361.078
|
| CAS # |
301692-76-2
|
| PubChem CID |
9841854
|
| Appearance |
Light yellow to green yellow solid powder
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
25
|
| Complexity |
672
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
IJWPAFMIFNSIGD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H16FNO4S/c1-18(2)17(21)15(12-4-3-5-13(19)10-12)16(24-18)11-6-8-14(9-7-11)25(20,22)23/h3-10H,1-2H3,(H2,20,22,23)
|
| Chemical Name |
4-[3-(3-fluorophenyl)-5,5-dimethyl-4-oxofuran-2-yl]benzenesulfonamide
|
| Synonyms |
CG 100649; CG-100649; CG100649
|
| 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 : ~250 mg/mL (~691.77 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.76 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7671 mL | 13.8355 mL | 27.6709 mL | |
| 5 mM | 0.5534 mL | 2.7671 mL | 5.5342 mL | |
| 10 mM | 0.2767 mL | 1.3835 mL | 2.7671 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
