For research use only. Not for therapeutic Use.
PF-04856264 is a potent, selective inhibitor of the human Nav1.7 voltage gated sodium channel (IC50 = 28 nM). The voltage-gated sodium channel NaV1.7 is preferentially expressed in peripheral somatic and visceral sensory neurons, olfactory sensory neurons and sympathetic ganglion neurons. NaV1.7 is a major contributor to pain signalling in humans, and homology modelling based on crystal structures of ion channels suggests an atomic-level structural basis for the altered gating of mutant NaV1.7 that causes pain.
| Catalog Number | I008665 |
| CAS Number | 1235397-05-3 |
| Synonyms | PF-04856264; PF04856264; PF 04856264; PF-4856264; PF4856264; PF 4856264.;3-cyano-4-(2-(1-methyl-1H-pyrazol-5-yl)phenoxy)-N-(thiazol-2-yl)benzenesulfonamide |
| Molecular Formula | C20H15N5O3S2 |
| Purity | ≥95% |
| Target | Sodium Channel |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | 3-cyano-4-[2-(2-methylpyrazol-3-yl)phenoxy]-N-(1,3-thiazol-2-yl)benzenesulfonamide |
| InChI | InChI=1S/C20H15N5O3S2/c1-25-17(8-9-23-25)16-4-2-3-5-19(16)28-18-7-6-15(12-14(18)13-21)30(26,27)24-20-22-10-11-29-20/h2-12H,1H3,(H,22,24) |
| InChIKey | MKSKJVIBSRUWSZ-UHFFFAOYSA-N |
| SMILES | CN1C(=CC=N1)C2=CC=CC=C2OC3=C(C=C(C=C3)S(=O)(=O)NC4=NC=CS4)C#N |
| Reference | 1:Toxins (Basel). 2016 Mar 17;8(3). pii: E78. doi: 10.3390/toxins8030078. Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain.Deuis JR,Wingerd JS,Winter Z,Durek T,Dekan Z,Sousa SR,Zimmermann K,Hoffmann T,Weidner C,Nassar MA,Alewood PF,Lewis RJ,Vetter I, PMID: 26999206 PMCID: PMC4810223 DOI: 10.3390/toxins8030078 </br><span>Abstract:</span> Loss-of-function mutations of Na(V)1.7 lead to congenital insensitivity to pain, a rare condition resulting in individuals who are otherwise normal except for the inability to sense pain, making pharmacological inhibition of Na(V)1.7 a promising therapeutic strategy for the treatment of pain. We characterized a novel mouse model of Na(V)1.7-mediated pain based on intraplantar injection of the scorpion toxin OD1, which is suitable for rapid in vivo profiling of Na(V)1.7 inhibitors. Intraplantar injection of OD1 caused spontaneous pain behaviors, which were reversed by co-injection with Na(V)1.7 inhibitors and significantly reduced in Na(V)1.7(-/-) mice. To validate the use of the model for profiling Na(V)1.7 inhibitors, we determined the Na(V) selectivity and tested the efficacy of the reported Na(V)1.7 inhibitors GpTx-1, PF-04856264 and CNV1014802 (raxatrigine). GpTx-1 selectively inhibited Na(V)1.7 and was effective when co-administered with OD1, but lacked efficacy when delivered systemically. PF-04856264 state-dependently and selectively inhibited Na(V)1.7 and significantly reduced OD1-induced spontaneous pain when delivered locally and systemically. CNV1014802 state-dependently, but non-selectively, inhibited Na(V) channels and was only effective in the OD1 model when delivered systemically. Our novel model of Na(V)1.7-mediated pain based on intraplantar injection of OD1 is thus suitable for the rapid in vivo characterization of the analgesic efficacy of Na(V)1.7 inhibitors. |
