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MedKoo Cat#: 522582 | Name: PF-04856264
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Description:

WARNING: This product is for research use only, not for human or veterinary 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.

Chemical Structure

PF-04856264
CAS# 1235397-05-3

Theoretical Analysis

MedKoo Cat#: 522582

Name: PF-04856264

CAS#: 1235397-05-3

Chemical Formula: C20H15N5O3S2

Exact Mass: 437.0616

Molecular Weight: 437.49

Elemental Analysis: C, 54.91; H, 3.46; N, 16.01; O, 10.97; S, 14.66

Price and Availability

Size Price Availability Quantity
5mg USD 270.00
25mg USD 720.00
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Synonym
PF-04856264; PF04856264; PF 04856264; PF-4856264; PF4856264; PF 4856264.
IUPAC/Chemical Name
3-cyano-4-(2-(1-methyl-1H-pyrazol-5-yl)phenoxy)-N-(thiazol-2-yl)benzenesulfonamide
InChi Key
MKSKJVIBSRUWSZ-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
O=S(C1=CC=C(OC2=CC=CC=C2C3=CC=NN3C)C(C#N)=C1)(NC4=NC=CS4)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-04856264 is a potent and selective Nav1.7 inhibitor, with IC50s of 28, 131, 19, and 42 nM for human, mouse, cynomolgus monkey and dog Nav1.7.
In vitro activity:
After pretreatment with PF-04856264, the number of action potentials elicited by depolarizing pulses was significantly less than that noted for five other cells exposed to PACAP alone (Fig. 5B). Thus this study concludes that PF-04856264 markedly attenuated the PACAP-induced increase in cardiac neuron excitability, an observation implicating PACAP/PAC1 receptor-mediated signaling in the regulation of Nav1.7. Reference: Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C643-C651. https://pubmed.ncbi.nlm.nih.gov/27488668/
In vivo activity:
Intraplantar injection of PF-04856264 concentration-dependently reduced spontaneous pain behaviors induced by co-administered OD1 (300 nM), although surprisingly, the high local concentrations required did not correlate with its in vitro potency (Figure 6D; spontaneous pain behaviors/10 min: control, 105 ± 6; PF-04856264 (1 mM), 19 ± 6; PF-04856264 (100 μM), 31 ± 8; PF-04856264 (10 μM), 81 ± 12; p < 0.05). Intraperitoneal administration of PF-04856264 was also effective (Figure 6E; spontaneous pain behaviors/10 min: control, 105 ± 6; PF-04856264 (30 mg/kg), 42 ± 8; p < 0.05) and well tolerated, with no significant motor adverse effects observed at doses up to 30 mg/kg, correlating well with the in vitro selectivity profile (Figure 5A; ataxia index: control, 2.7 ± 0.4; PF-04856264 (30 mg/kg), 4.6 ± 1.3; p > 0.05; Figure 5B; distance travelled: control, 1.49 ± 0.16 m; PF-04856264 (30 mg/kg), 1.03 ± 0.17 m; p > 0.05). Reference: Toxins (Basel). 2016 Mar 17;8(3):78. https://pubmed.ncbi.nlm.nih.gov/26999206/
Solvent mg/mL mM comments
Solubility
DMSO 250.0 571.44
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 437.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Tompkins JD, Clason TA, Hardwick JC, Girard BM, Merriam LA, May V, Parsons RL. Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability. Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C643-C651. doi: 10.1152/ajpcell.00164.2016. Epub 2016 Aug 3. PMID: 27488668; PMCID: PMC5129752. 2. 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. Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain. Toxins (Basel). 2016 Mar 17;8(3):78. doi: 10.3390/toxins8030078. PMID: 26999206; PMCID: PMC4810223.
In vitro protocol:
1. Tompkins JD, Clason TA, Hardwick JC, Girard BM, Merriam LA, May V, Parsons RL. Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability. Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C643-C651. doi: 10.1152/ajpcell.00164.2016. Epub 2016 Aug 3. PMID: 27488668; PMCID: PMC5129752.
In vivo protocol:
1. 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. Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain. Toxins (Basel). 2016 Mar 17;8(3):78. doi: 10.3390/toxins8030078. PMID: 26999206; PMCID: PMC4810223.
1: Tian JJ, Tan CY, Chen QY, Zhou Y, Qu ZW, Zhang M, Ma KT, Shi WY, Li L, Si JQ. Upregulation of Nav1.7 by endogenous hydrogen sulfide contributes to maintenance of neuropathic pain. Int J Mol Med. 2020 Aug;46(2):782-794. doi: 10.3892/ijmm.2020.4611. Epub 2020 May 20. PMID: 32468069; PMCID: PMC7307826. 2: Mueller A, Starobova H, Morgan M, Dekan Z, Cheneval O, Schroeder CI, Alewood PF, Deuis JR, Vetter I. Antiallodynic effects of the selective NaV1.7 inhibitor Pn3a in a mouse model of acute postsurgical pain: evidence for analgesic synergy with opioids and baclofen. Pain. 2019 Aug;160(8):1766-1780. doi: 10.1097/j.pain.0000000000001567. PMID: 31335646. 3: Yoshizawa K, Arai N, Suzuki Y, Nakamura T, Takeuchi K, Sakamoto R, Masuda R. Evaluation of the antinociceptive activities of several sodium channel blockers using veratrine test in mice. Synapse. 2018 Jul 11. doi: 10.1002/syn.22056. Epub ahead of print. PMID: 29993143. 4: Zhao F, Jin W, Ma L, Zhang JY, Wang JL, Zhang JH, Song YB. Investigation of the selectivity of one type of small-molecule inhibitor for three Nav channel isoforms based on the method of computer simulation. J Biomol Struct Dyn. 2019 Feb;37(3):702-713. doi: 10.1080/07391102.2018.1438921. Epub 2018 Feb 16. PMID: 29448911. 5: Deuis JR, Dekan Z, Wingerd JS, Smith JJ, Munasinghe NR, Bhola RF, Imlach WL, Herzig V, Armstrong DA, Rosengren KJ, Bosmans F, Waxman SG, Dib-Hajj SD, Escoubas P, Minett MS, Christie MJ, King GF, Alewood PF, Lewis RJ, Wood JN, Vetter I. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883. Erratum in: Sci Rep. 2017 May 26;7:46816. doi: 10.1038/srep46816. PMID: 28106092; PMCID: PMC5247677. 6: Tompkins JD, Clason TA, Hardwick JC, Girard BM, Merriam LA, May V, Parsons RL. Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability. Am J Physiol Cell Physiol. 2016 Oct 1;311(4):C643-C651. doi: 10.1152/ajpcell.00164.2016. Epub 2016 Aug 3. PMID: 27488668; PMCID: PMC5129752. 7: Zhang H, Reichert E, Cohen AE. Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels. Elife. 2016 May 24;5:e15202. doi: 10.7554/eLife.15202. PMID: 27215841; PMCID: PMC4907688. 8: 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. Analgesic Effects of GpTx-1, PF-04856264 and CNV1014802 in a Mouse Model of NaV1.7-Mediated Pain. Toxins (Basel). 2016 Mar 17;8(3):78. doi: 10.3390/toxins8030078. PMID: 26999206; PMCID: PMC4810223. 9: McCormack K, Santos S, Chapman ML, Krafte DS, Marron BE, West CW, Krambis MJ, Antonio BM, Zellmer SG, Printzenhoff D, Padilla KM, Lin Z, Wagoner PK, Swain NA, Stupple PA, de Groot M, Butt RP, Castle NA. Voltage sensor interaction site for selective small molecule inhibitors of voltage-gated sodium channels. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):E2724-32. doi: 10.1073/pnas.1220844110. Epub 2013 Jul 1. PMID: 23818614; PMCID: PMC3718154.