SB-705498
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MedKoo CAT#: 526766

CAS#: 501951-42-4

Description: SB-705498 is an orally bioavailable, competitive antagonist of the capsaicin-mediated activation of TRPV1 receptors (pKis = 7.6, 7.5, and 7.3 for human, rat, and guinea pig, respectively). SB-705498 inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor. SB-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the human TRPV1 receptor (pK(i) = 7.6) with activity at rat (pK(i) = 7.5) and guinea pig (pK(i) = 7.3) orthologs.

Chemical Structure

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SB-705498
CAS# 501951-42-4
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526766
Name: SB-705498
CAS#: 501951-42-4
Chemical Formula: C17H16BrF3N4O
Exact Mass: 428.05
Molecular Weight: 429.240
Elemental Analysis: C, 47.57; H, 3.76; Br, 18.62; F, 13.28; N, 13.05; O, 3.73

Price and Availability

Size Price Availability Quantity
50mg USD 285 2 Weeks
100mg USD 500 2 Weeks
250mg USD 950 2 Weeks
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Synonym: SB-705498; SB 705498; SB705498.

IUPAC/Chemical Name: N-(2-bromophenyl)-N'-[(3R)-1-[5-(trifluoromethyl)-2-pyridinyl]-3-pyrrolidinyl]-urea

InChi Key: JYILLRHXRVTRSH-GFCCVEGCSA-N

InChi Code: InChI=1S/C17H16BrF3N4O/c18-13-3-1-2-4-14(13)24-16(26)23-12-7-8-25(10-12)15-6-5-11(9-22-15)17(19,20)21/h1-6,9,12H,7-8,10H2,(H2,23,24,26)/t12-/m1/s1

SMILES Code: O=C(N[C@H]1CN(C2=NC=C(C(F)(F)F)C=C2)CC1)NC3=CC=CC=C3Br

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).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
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Biological target: SB-705498 is an antagonist of the capsaicin-mediated activation of TRPV1 receptors (pKis = 7.6, 7.5, and 7.3 for human, rat, and guinea pig, respectively). SB-705498 inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor.
In vitro activity: SB-705498 displayed potent and selective inhibitory action against the capsaicin-mediated activation of TRPV1 receptor orthologs. SB-705498 demonstrated rapid and reversible inhibition of TRPV1 activation by capsaicin, acid, and heat. It exhibited some voltage-dependent characteristics, indicating potential efficacy in neuronal conditions. Reference: J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. https://pubmed.ncbi.nlm.nih.gov/17392405/
In vivo activity: SB-705498 as a therapeutic option for rhinitis, especially when administered intranasally with optimized formulation. Intranasal administration of SB-705498 reduced capsaicin-induced contralateral nasal secretions. Oral and intranasal administration of SB-705498 resulted in a notable reduction in secretory responses. Reference: Br J Pharmacol. 2013 Jun;169(3):580-9. https://pubmed.ncbi.nlm.nih.gov/23441756/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 232.98

Preparing Stock Solutions

The following data is based on the product molecular weight 429.24 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. Gunthorpe MJ, Hannan SL, Smart D, Jerman JC, Arpino S, Smith GD, Brough S, Wright J, Egerton J, Lappin SC, Holland VA, Winborn K, Thompson M, Rami HK, Randall A, Davis JB. Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor. J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. doi: 10.1124/jpet.106.116657. Epub 2007 Mar 28. PMID: 17392405. 2. Rami HK, Thompson M, Stemp G, Fell S, Jerman JC, Stevens AJ, Smart D, Sargent B, Sanderson D, Randall AD, Gunthorpe MJ, Davis JB. Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3287-91. doi: 10.1016/j.bmcl.2006.03.030. Epub 2006 Mar 31. PMID: 16580202. 3. Changani K, Hotee S, Campbell S, Pindoria K, Dinnewell L, Saklatvala P, Thompson SA, Coe D, Biggadike K, Vitulli G, Lines M, Busza A, Denyer J. Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig. Br J Pharmacol. 2013 Jun;169(3):580-9. doi: 10.1111/bph.12145. PMID: 23441756; PMCID: PMC3682706. 4. Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain. 2007 Nov;132(1-2):132-41. doi: 10.1016/j.pain.2007.06.006. Epub 2007 Jul 30. PMID: 17659837.
In vitro protocol: 1. Gunthorpe MJ, Hannan SL, Smart D, Jerman JC, Arpino S, Smith GD, Brough S, Wright J, Egerton J, Lappin SC, Holland VA, Winborn K, Thompson M, Rami HK, Randall A, Davis JB. Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor. J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. doi: 10.1124/jpet.106.116657. Epub 2007 Mar 28. PMID: 17392405. 2. Rami HK, Thompson M, Stemp G, Fell S, Jerman JC, Stevens AJ, Smart D, Sargent B, Sanderson D, Randall AD, Gunthorpe MJ, Davis JB. Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development. Bioorg Med Chem Lett. 2006 Jun 15;16(12):3287-91. doi: 10.1016/j.bmcl.2006.03.030. Epub 2006 Mar 31. PMID: 16580202.
In vivo protocol: 1. Changani K, Hotee S, Campbell S, Pindoria K, Dinnewell L, Saklatvala P, Thompson SA, Coe D, Biggadike K, Vitulli G, Lines M, Busza A, Denyer J. Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig. Br J Pharmacol. 2013 Jun;169(3):580-9. doi: 10.1111/bph.12145. PMID: 23441756; PMCID: PMC3682706. 2. Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain. 2007 Nov;132(1-2):132-41. doi: 10.1016/j.pain.2007.06.006. Epub 2007 Jul 30. PMID: 17659837.

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1: Gibson RA, Robertson J, Mistry H, McCallum S, Fernando D, Wyres M, Yosipovitch G. A randomised trial evaluating the effects of the TRPV1 antagonist SB705498 on pruritus induced by histamine, and cowhage challenge in healthy volunteers. PLoS One. 2014 Jul 21;9(7):e100610. doi: 10.1371/journal.pone.0100610. eCollection 2014. PubMed PMID: 25047038; PubMed Central PMCID: PMC4105653.

2: Khalid S, Murdoch R, Newlands A, Smart K, Kelsall A, Holt K, Dockry R, Woodcock A, Smith JA. Transient receptor potential vanilloid 1 (TRPV1) antagonism in patients with refractory chronic cough: a double-blind randomized controlled trial. J Allergy Clin Immunol. 2014 Jul;134(1):56-62. doi: 10.1016/j.jaci.2014.01.038. Epub 2014 Mar 22. PubMed PMID: 24666696.

3: Murdoch RD, Bareille P, Denyer J, Newlands A, Bentley J, Smart K, Yarnall K, Patel D. TRPV1 inhibition does not prevent cold dry air-elicited symptoms in non-allergic rhinitis. Int J Clin Pharmacol Ther. 2014 Apr;52(4):267-76. doi: 10.5414/CP202013. PubMed PMID: 24472402.

4: Holland C, van Drunen C, Denyer J, Smart K, Segboer C, Terreehorst I, Newlands A, Beerahee M, Fokkens W, Tsitoura DC. Inhibition of capsaicin-driven nasal hyper-reactivity by SB-705498, a TRPV1 antagonist. Br J Clin Pharmacol. 2014 May;77(5):777-88. doi: 10.1111/bcp.12219. PubMed PMID: 23909699; PubMed Central PMCID: PMC4004398.

5: Bareille P, Murdoch RD, Denyer J, Bentley J, Smart K, Yarnall K, Zieglmayer P, Zieglmayer R, Lemell P, Horak F. The effects of a TRPV1 antagonist, SB-705498, in the treatment of seasonal allergic rhinitis. Int J Clin Pharmacol Ther. 2013 Jul;51(7):576-84. doi: 10.5414/CP201890. PubMed PMID: 23735181.

6: Changani K, Hotee S, Campbell S, Pindoria K, Dinnewell L, Saklatvala P, Thompson SA, Coe D, Biggadike K, Vitulli G, Lines M, Busza A, Denyer J. Effect of the TRPV1 antagonist SB-705498 on the nasal parasympathetic reflex response in the ovalbumin sensitized guinea pig. Br J Pharmacol. 2013 Jun;169(3):580-9. doi: 10.1111/bph.12145. PubMed PMID: 23441756; PubMed Central PMCID: PMC3682706.

7: Psachoulias D, Vertzoni M, Butler J, Busby D, Symillides M, Dressman J, Reppas C. An in vitro methodology for forecasting luminal concentrations and precipitation of highly permeable lipophilic weak bases in the fasted upper small intestine. Pharm Res. 2012 Dec;29(12):3486-98. doi: 10.1007/s11095-012-0844-z. Epub 2012 Aug 14. PubMed PMID: 22890986.

8: Kort ME, Kym PR. TRPV1 antagonists: clinical setbacks and prospects for future development. Prog Med Chem. 2012;51:57-70. doi: 10.1016/B978-0-12-396493-9.00002-9. Review. PubMed PMID: 22520471.

9: Delescluse I, Mace H, Adcock JJ. Inhibition of airway hyper-responsiveness by TRPV1 antagonists (SB-705498 and PF-04065463) in the unanaesthetized, ovalbumin-sensitized guinea pig. Br J Pharmacol. 2012 Jul;166(6):1822-32. doi: 10.1111/j.1476-5381.2012.01891.x. PubMed PMID: 22320181; PubMed Central PMCID: PMC3402807.

10: Alenmyr L, Greiff L, Andersson M, Sterner O, Zygmunt PM, Högestätt ED. Effect of mucosal TRPV1 inhibition in allergic rhinitis. Basic Clin Pharmacol Toxicol. 2012 Mar;110(3):264-8. doi: 10.1111/j.1742-7843.2011.00803.x. Epub 2011 Oct 25. PubMed PMID: 21951314.

11: Tékus V, Bölcskei K, Kis-Varga A, Dézsi L, Szentirmay E, Visegrády A, Horváth C, Szolcsányi J, Petho G. Effect of transient receptor potential vanilloid 1 (TRPV1) receptor antagonist compounds SB705498, BCTC and AMG9810 in rat models of thermal hyperalgesia measured with an increasing-temperature water bath. Eur J Pharmacol. 2010 Sep 1;641(2-3):135-41. doi: 10.1016/j.ejphar.2010.05.052. Epub 2010 Jun 8. PubMed PMID: 20534382.

12: Lambert GA, Davis JB, Appleby JM, Chizh BA, Hoskin KL, Zagami AS. The effects of the TRPV1 receptor antagonist SB-705498 on trigeminovascular sensitisation and neurotransmission. Naunyn Schmiedebergs Arch Pharmacol. 2009 Oct;380(4):311-25. doi: 10.1007/s00210-009-0437-5. Epub 2009 Aug 19. PubMed PMID: 19690836.

13: van den Wijngaard RM, Klooker TK, Welting O, Stanisor OI, Wouters MM, van der Coelen D, Bulmer DC, Peeters PJ, Aerssens J, de Hoogt R, Lee K, de Jonge WJ, Boeckxstaens GE. Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. Neurogastroenterol Motil. 2009 Oct;21(10):1107-e94. doi: 10.1111/j.1365-2982.2009.01339.x. Epub 2009 Jun 11. PubMed PMID: 19523146.

14: Kym PR, Kort ME, Hutchins CW. Analgesic potential of TRPV1 antagonists. Biochem Pharmacol. 2009 Aug 1;78(3):211-6. doi: 10.1016/j.bcp.2009.02.014. Epub 2009 Mar 5. PubMed PMID: 19481638.

15: van den Wijngaard RM, Welting O, Bulmer DC, Wouters MM, Lee K, de Jonge WJ, Boeckxstaens GE. Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat. Neurogastroenterol Motil. 2009 Aug;21(8):863-e60. doi: 10.1111/j.1365-2982.2009.01287.x. Epub 2009 Mar 9. PubMed PMID: 19298229.

16: Lambert DG. Capsaicin receptor antagonists: a promising new addition to the pain clinic. Br J Anaesth. 2009 Feb;102(2):153-5. doi: 10.1093/bja/aen354. PubMed PMID: 19151045.

17: Wong GY, Gavva NR. Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks. Brain Res Rev. 2009 Apr;60(1):267-77. doi: 10.1016/j.brainresrev.2008.12.006. Epub 2008 Dec 25. Review. PubMed PMID: 19150372.

18: Conway SJ. TRPing the switch on pain: an introduction to the chemistry and biology of capsaicin and TRPV1. Chem Soc Rev. 2008 Aug;37(8):1530-45. doi: 10.1039/b610226n. Epub 2008 Jun 20. Review. PubMed PMID: 18648679.

19: Chizh BA, O'Donnell MB, Napolitano A, Wang J, Brooke AC, Aylott MC, Bullman JN, Gray EJ, Lai RY, Williams PM, Appleby JM. The effects of the TRPV1 antagonist SB-705498 on TRPV1 receptor-mediated activity and inflammatory hyperalgesia in humans. Pain. 2007 Nov;132(1-2):132-41. Epub 2007 Jul 30. PubMed PMID: 17659837.

20: Gunthorpe MJ, Hannan SL, Smart D, Jerman JC, Arpino S, Smith GD, Brough S, Wright J, Egerton J, Lappin SC, Holland VA, Winborn K, Thompson M, Rami HK, Randall A, Davis JB. Characterization of SB-705498, a potent and selective vanilloid receptor-1 (VR1/TRPV1) antagonist that inhibits the capsaicin-, acid-, and heat-mediated activation of the receptor. J Pharmacol Exp Ther. 2007 Jun;321(3):1183-92. Epub 2007 Mar 28. PubMed PMID: 17392405.