For research use only. Not for therapeutic Use.
PF-05089771 (Cat No.:I000939) is an active metabolite of Roflumilast used in the treatment of chronic obstructive pulmonary disease (COPD). This compound inhibits the enzyme phosphodiesterase-4 (PDE-4), reducing inflammation and promoting bronchodilation. Administered orally, PF-05089771 exhibits anti-inflammatory properties and helps alleviate symptoms of COPD.
| Catalog Number | I000939 |
| CAS Number | 1235403-62-9 |
| Molecular Formula | C18H12Cl2FN5O3S2 |
| Purity | ≥95% |
| Target | Nav1.7 Inhibitor |
| Solubility | DMSO: ≥ 34 mg/mL |
| Storage | Store at -20°C |
| IUPAC Name | 4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-(1,3-thiazol-4-yl)benzenesulfonamide |
| InChI | InChI=1S/C18H12Cl2FN5O3S2/c19-9-1-2-14(10(3-9)11-6-24-25-18(11)22)29-15-5-13(21)16(4-12(15)20)31(27,28)26-17-7-30-8-23-17/h1-8,26H,(H3,22,24,25) |
| InChIKey | ZYSCOUXLBXGGIM-UHFFFAOYSA-N |
| SMILES | C1=CC(=C(C=C1Cl)C2=C(NN=C2)N)OC3=CC(=C(C=C3Cl)S(=O)(=O)NC4=CSC=N4)F |
| Reference | 1:Mol Pharmacol. 2016 Nov;90(5):540-548. Epub 2016 Sep 1. The Selective Nav1.7 Inhibitor, PF-05089771, Interacts Equivalently with Fast and Slow Inactivated Nav1.7 Channels.Theile JW,Fuller MD,Chapman ML, PMID: 27587537 DOI: 10.1124/mol.116.105437 </br><span>Abstract:</span> Voltage-gated sodium (Nav) channel inhibitors are used clinically as analgesics and local anesthetics. However, the absence of Nav channel isoform selectivity of current treatment options can result in adverse cardiac and central nervous system side effects, limiting their therapeutic utility. Human hereditary gain- or loss-of-pain disorders have demonstrated an essential role of Nav1.7 sodium channels in the sensation of pain, thus making this channel an attractive target for new pain therapies. We previously identified a novel, state-dependent human Nav1.7 selective inhibitor (PF-05089771, IC50 = 11 nM) that interacts with the voltage-sensor domain (VSD) of domain IV. We further characterized the state-dependent interaction of PF-05089771 by systematically varying the voltage, frequency, and duration of conditioning prepulses to provide access to closed, open, and fast- or slow-inactivated states. The current study demonstrates that PF-05089771 exhibits a slow onset of block that is depolarization and concentration dependent, with a similarly slow recovery from block. Furthermore, the onset of block by PF-05089771 develops with similar rates using protocols that bias channels into predominantly fast- or slow-inactivated states, suggesting that channel inhibition is less dependent on the availability of a particular inactivated state than the relative time that the channel is depolarized. Taken together, the inhibitory profile of PF-05089771 suggests that a conformational change in the domain IV VSD after depolarization is necessary and sufficient to reveal a high-affinity binding site with which PF-05089771 interacts, stabilizing the channel in a nonconducting conformation from which recovery is slow.Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics. |
