NaV1.7 Blocker-13

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

MedKoo CAT#: 525626

CAS#: N/A

Description: NaV1.7 Blocker-13 is a novel selective blocker of NaV1.7 with little affinity for NaV 1.2, 1.3, or 1.6, being more potent at human vs guinea pig NaV1.7.


Price and Availability

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NaV1.7 Blocker-13 is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 525626
Name: NaV1.7 Blocker-13
CAS#: N/A
Chemical Formula: C21H15ClF4N6O3S2
Exact Mass: 574.0272
Molecular Weight: 574.9536
Elemental Analysis: C, 43.87; H, 2.63; Cl, 6.17; F, 13.22; N, 14.62; O, 8.35; S, 11.15


Synonym: NaV1.7 Blocker-13

IUPAC/Chemical Name: 4-[2-(2-Azetidin-3-yl-2H-pyrazol-3-yl)-4-trifluoromethyl-phenoxy]-5-chloro-2-fluoro-N-[1,2,4]thiadiazol-5-yl-benzenesulfonamide

InChi Key: SIEHVRLODLAMBZ-UHFFFAOYSA-N

InChi Code: InChI=1S/C21H15ClF4N6O3S2/c22-14-6-19(37(33,34)31-20-28-10-30-36-20)15(23)7-18(14)35-17-2-1-11(21(24,25)26)5-13(17)16-3-4-29-32(16)12-8-27-9-12/h1-7,10,12,27H,8-9H2,(H,28,30,31)

SMILES Code: O=S(C1=CC(Cl)=C(OC2=CC=C(C(F)(F)F)C=C2C3=CC=NN3C4CNC4)C=C1F)(NC5=NC=NS5)=O


Technical Data

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

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).

Harmonized System Code:
293490


References

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2: Sun H, Kollarik M, Undem BJ. Blocking voltage-gated sodium channels as a strategy to suppress pathological cough. Pulm Pharmacol Ther. 2017 May 15. pii: S1094-5539(17)30112-8. doi: 10.1016/j.pupt.2017.05.010. [Epub ahead of print] Review. PubMed PMID: 28522215.

3: Zhang X, Priest BT, Belfer I, Gold MS. Voltage-gated Na(+) currents in human dorsal root ganglion neurons. Elife. 2017 May 16;6. pii: e23235. doi: 10.7554/eLife.23235. PubMed PMID: 28508747; PubMed Central PMCID: PMC5433841.

4: Low SA, Robbins W, Tawfik VL. Complex management of a patient with refractory primary erythromelalgia lacking a SCN9A mutation. J Pain Res. 2017 Apr 27;10:973-977. doi: 10.2147/JPR.S129661. eCollection 2017. PubMed PMID: 28490900; PubMed Central PMCID: PMC5414616.

5: Berta T, Qadri Y, Tan PH, Ji RR. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain. Expert Opin Ther Targets. 2017 May 16:1-9. doi: 10.1080/14728222.2017.1328057. [Epub ahead of print] PubMed PMID: 28480765.

6: Kornecook TJ, Yin R, Altmann S, Be X, Berry V, Ilch CP, Jarosh M, Johnson D, Lee JH, Lehto SG, Ligutti J, Liu D, Luther J, Matson D, Ortuno D, Roberts J, Taborn K, Wang J, Weiss MM, Yu V, Zhu DXD, Fremeau RT, Moyer BD. Pharmacologic Characterization of AMG8379, a Potent and Selective Small Molecule Sulfonamide Antagonist of the Voltage-Gated Sodium Channel Na(V)1.7. J Pharmacol Exp Ther. 2017 May 4. pii: jpet.116.239590. doi: 10.1124/jpet.116.239590. [Epub ahead of print] PubMed PMID: 28473457.

7: Pero JE, Rossi MA, Lehman HDGF, Kelly MJ 3rd, Mulhearn JJ, Wolkenberg SE, Cato MJ, Clements MK, Daley CJ, Filzen T, Finger EN, Gregan Y, Henze DA, Jovanovska A, Klein R, Kraus RL, Li Y, Liang A, Majercak JM, Panigel J, Urban MO, Wang J, Wang YH, Houghton AK, Layton ME. Benzoxazolinone aryl sulfonamides as potent, selective Na(v)1.7 inhibitors with in vivo efficacy in a preclinical pain model. Bioorg Med Chem Lett. 2017 Apr 22. pii: S0960-894X(17)30417-1. doi: 10.1016/j.bmcl.2017.04.040. [Epub ahead of print] PubMed PMID: 28465103.

8: Klein AH, Vyshnevska A, Hartke TV, De Col R, Mankowski JL, Turnquist B, Bosmans F, Reeh PW, Schmelz M, Carr RW, Ringkamp M. Sodium Channel Na(v)1.8 Underlies TTX-Resistant Axonal Action Potential Conduction in Somatosensory C-Fibers of Distal Cutaneous Nerves. J Neurosci. 2017 May 17;37(20):5204-5214. doi: 10.1523/JNEUROSCI.3799-16.2017. Epub 2017 Apr 27. PubMed PMID: 28450535.

9: Yen LT, Hsieh CL, Hsu HC, Lin YW. Targeting ASIC3 for Relieving Mice Fibromyalgia Pain: Roles of Electroacupuncture, Opioid, and Adenosine. Sci Rep. 2017 Apr 25;7:46663. doi: 10.1038/srep46663. PubMed PMID: 28440280; PubMed Central PMCID: PMC5404229.

10: Chang W, Berta T, Kim YH, Lee S, Lee SY, Ji RR. Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel. Neurosci Bull. 2017 Apr 19. doi: 10.1007/s12264-017-0132-3. [Epub ahead of print] PubMed PMID: 28424991.

11: Bolz F, Kasper S, Bufe B, Zufall F, Pyrski M. Organization and Plasticity of Sodium Channel Expression in the Mouse Olfactory and Vomeronasal Epithelia. Front Neuroanat. 2017 Apr 3;11:28. doi: 10.3389/fnana.2017.00028. eCollection 2017. PubMed PMID: 28420967; PubMed Central PMCID: PMC5376585.

12: Sema3A signalling requires CRMP1 and Na(v)1.7. J Cell Sci. 2017 Apr 15;130(8):e0802. PubMed PMID: 28412697.

13: Langlois V, Bedat Millet AL, Lebesnerais M, Miranda S, Marguet F, Benhamou Y, Marcorelles P, Lévesque H. [Small fiber neuropathy]. Rev Med Interne. 2017 Apr 11. pii: S0248-8663(17)30106-6. doi: 10.1016/j.revmed.2017.03.013. [Epub ahead of print] French. PubMed PMID: 28410768.

14: Roecker AJ, Egbertson M, Jones KLG, Gomez R, Kraus RL, Li Y, Koser AJ, Urban MO, Klein R, Clements M, Panigel J, Daley C, Wang J, Finger EN, Majercak J, Santarelli V, Gregan I, Cato M, Filzen T, Jovanovska A, Wang YH, Wang D, Joyce LA, Sherer EC, Peng X, Wang X, Sun H, Coleman PJ, Houghton AK, Layton ME. Discovery of selective, orally bioavailable, N-linked arylsulfonamide Na(v)1.7 inhibitors with pain efficacy in mice. Bioorg Med Chem Lett. 2017 May 15;27(10):2087-2093. doi: 10.1016/j.bmcl.2017.03.085. Epub 2017 Mar 30. PubMed PMID: 28389149.

15: Tanaka BS, Nguyen PT, Zhou EY, Yang Y, Yarov-Yarovoy V, Dib-Hajj SD, Waxman SG. Gain-of-Function Mutation of a Voltage-Gated Sodium Channel Na(V)1.7 Associated with Peripheral Pain and Impaired Limb Development. J Biol Chem. 2017 Apr 5. pii: jbc.M117.778779. doi: 10.1074/jbc.M117.778779. [Epub ahead of print] PubMed PMID: 28381558.

16: Cruccu G. Trigeminal Neuralgia. Continuum (Minneap Minn). 2017 Apr;23(2, Selected Topics in Outpatient Neurology):396-420. doi: 10.1212/CON.0000000000000451. PubMed PMID: 28375911.

17: Zhang P, Gan YH. Prostaglandin E(2) Upregulated Trigeminal Ganglionic Sodium Channel 1.7 Involving Temporomandibular Joint Inflammatory Pain in Rats. Inflammation. 2017 Jun;40(3):1102-1109. doi: 10.1007/s10753-017-0552-2. PubMed PMID: 28349234.

18: Marx IE, Dineen TA, Able J, Bode C, Bregman H, Chu-Moyer M, DiMauro EF, Du B, Foti RS, Fremeau RT Jr, Gao H, Gunaydin H, Hall BE, Huang L, Kornecook T, Kreiman CR, La DS, Ligutti J, Lin MJ, Liu D, McDermott JS, Moyer BD, Nguyen HN, Peterson EA, Roberts JT, Rose P, Wang J, Youngblood BD, Yu V, Weiss MM. Correction to "Sulfonamides as Selective Na(V)1.7 Inhibitors: Optimizing Potency and Pharmacokinetics to Enable in Vivo Target Engagement". ACS Med Chem Lett. 2017 Feb 28;8(3):378. doi: 10.1021/acsmedchemlett.7b00075. eCollection 2017 Mar 9. PubMed PMID: 28337335; PubMed Central PMCID: PMC5346988.

19: Graceffa RF, Boezio AA, Able J, Altmann S, Berry LM, Boezio C, Butler JR, Chu-Moyer M, Cooke M, DiMauro EF, Dineen TA, Feric Bojic E, Foti RS, Fremeau RT Jr, Guzman-Perez A, Gao H, Gunaydin H, Huang H, Huang L, Ilch C, Jarosh M, Kornecook T, Kreiman CR, La DS, Ligutti J, Milgram BC, Lin MJ, Marx IE, Nguyen HN, Peterson EA, Rescourio G, Roberts J, Schenkel L, Shimanovich R, Sparling BA, Stellwagen J, Taborn K, Vaida KR, Wang J, Yeoman J, Yu V, Zhu D, Moyer BD, Weiss MM. Sulfonamides as Selective Na(V)1.7 Inhibitors: Optimizing Potency, Pharmacokinetics, and Metabolic Properties to Obtain Atropisomeric Quinolinone (AM-0466) that Affords Robust in Vivo Activity. J Med Chem. 2017 Apr 20. doi: 10.1021/acs.jmedchem.6b01850. [Epub ahead of print] PubMed PMID: 28324649.

20: Rahnama S, Deuis JR, Cardoso FC, Ramanujam V, Lewis RJ, Rash LD, King GF, Vetter I, Mobli M. The structure, dynamics and selectivity profile of a NaV1.7 potency-optimised huwentoxin-IV variant. PLoS One. 2017 Mar 16;12(3):e0173551. doi: 10.1371/journal.pone.0173551. eCollection 2017. PubMed PMID: 28301520; PubMed Central PMCID: PMC5354290.