For research use only. Not for therapeutic Use.
Polmacoxib (CAT: I008824), also known as CG100649, is a pioneering NSAID drug candidate that uniquely targets both COX-2 and carbonic anhydrase (CA), offering potential advantages in safety and efficacy. Its interaction with CA in red blood cells facilitates selective tissue transport, delivering sustained anti-inflammatory levels to inflamed tissues while minimizing systemic exposure. This innovative approach aims to enhance therapeutic benefits while reducing risks to cardiovascular, renal, and gastrointestinal tissues. Polmacoxib’s dual inhibition properties extend its potential applications, including inhibiting colorectal lesions and tumor cell proliferation in mouse models, making it a promising candidate in both pain management and cancer research.
| Catalog Number | I008824 |
| CAS Number | 301692-76-2 |
| Synonyms | ;4-(3-(3-fluorophenyl)-5,5-dimethyl-4-oxo-4,5-dihydrofuran-2-yl)benzenesulfonamide |
| Molecular Formula | C18H16FNO4S |
| Purity | ≥95% |
| Target | Metabolic Enzyme/Protease |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | 4-[3-(3-fluorophenyl)-5,5-dimethyl-4-oxofuran-2-yl]benzenesulfonamide |
| InChI | 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) |
| InChIKey | IJWPAFMIFNSIGD-UHFFFAOYSA-N |
| SMILES | CC1(C(=O)C(=C(O1)C2=CC=C(C=C2)S(=O)(=O)N)C3=CC(=CC=C3)F)C |
| Reference | 1:Biochem Biophys Res Commun. 2016 Sep 9;478(1):1-6. doi: 10.1016/j.bbrc.2016.07.114. Epub 2016 Jul 27. Structural insight into the inhibition of carbonic anhydrase by the COX-2-selective inhibitor polmacoxib (CG100649).Kim HT,Cha H,Hwang KY, PMID: 27475498 DOI: 10.1016/j.bbrc.2016.07.114 </br><span>Abstract:</span> Polmacoxib is not only a selective COX-2 inhibitor but also a potent inhibitor of carbonic anhydrases (CAs). Both CA I and CA II are highly expressed in the GI tract and kidneys, organs that are also thought to be the sites at which selective COX-2 inhibitors show their side effects. By inhibition assays, we show that both CA I and CA II are strongly inhibited by polmacoxib, while CA II also demonstrates direct competition with COX-2. To understand, at the molecular level, how polmacoxib interacts with CA I and II, we solved the first crystal structures of CA I and CA II in complex with polmacoxib, at 2.0 Å and 1.8 Å, respectively. Interestingly, three polmacoxib molecules bind to the active site of CA I, whereas only one molecule binds CA II. In the active site, the three molecules of polmacoxib organize itself along hydrophobic interaction as /stack-on-formation/, and fully occupy a cone-shaped active pocket in CA I. The binding mode of polmacoxib to CA II was found different than its binding to celecoxib and valdecoxib. Our results provide structural insight into inhibition of CA I and CA II by polmacoxib, to assess its potential clinical efficacy. Copyright © 2016 Elsevier Inc. All rights reserved. |
