SB-705498 | CAS#501951-42-4 | TRPV1 receptor

MedKoo Cat#: 526766 | Name: SB-705498

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Description:

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

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

SB-705498

CAS#501951-42-4

Theoretical Analysis

MedKoo Cat#: 526766

Name: SB-705498

CAS#: 501951-42-4

Chemical Formula: C17H16BrF3N4O

Exact Mass: 428.0460

Molecular Weight: 429.24

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
50mg	USD 350.00	2 Weeks
100mg	USD 600.00	2 Weeks
250mg	USD 1,050.00	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

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Product Data

Product Data

Instruction

View handling instruction

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	100.0	232.98

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 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.

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:

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.

1: 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. PMID: 23735181. 2: 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. PMID: 23909699; PMCID: PMC4004398. 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: 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. 5: 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. PMID: 19690836. 6: 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. 7: 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. 8: 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. PMID: 24472402. 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. PMID: 22320181; PMCID: PMC3402807. 10: 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. PMID: 19481638. 11: Yang Z, Zhou Z, Si T, Zhou Z, Zhou L, Chin YR, Zhang L, Guan X, Yang M. High Throughput Confined Migration Microfluidic Device for Drug Screening. Small. 2023 Apr;19(16):e2207194. doi: 10.1002/smll.202207194. Epub 2023 Jan 12. PMID: 36634971. 12: 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. PMID: 21951314. 13: Belvisi MG, Birrell MA, Wortley MA, Maher SA, Satia I, Badri H, Holt K, Round P, McGarvey L, Ford J, Smith JA. XEN-D0501, a Novel Transient Receptor Potential Vanilloid 1 Antagonist, Does Not Reduce Cough in Patients with Refractory Cough. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1255-1263. doi: 10.1164/rccm.201704-0769OC. PMID: 28650204. 14: Qiao Y, Zhang Y, Qiao Z, He W, Chen Y, Song D, Wang G, Guo N, Shao L, Tian Z, Wang Q, Yan L, Qian H. Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist. Eur J Med Chem. 2022 Apr 5;233:114191. doi: 10.1016/j.ejmech.2022.114191. Epub 2022 Feb 21. PMID: 35263708. 15: Ling X, Wang W. A-80426 suppresses CFA-induced inflammatory pain by suppressing TRPV1 activity via NFκB and PI3K pathways in mice. Clinics (Sao Paulo). 2023 Jun 1;78:100213. doi: 10.1016/j.clinsp.2023.100213. PMID: 37269788; PMCID: PMC10248075. 16: Gujarati NA, Undem BJ, Korlipara VL. Design, Synthesis, and Evaluation of Isoquinoline Ureas as TRPV1 Antagonists. Med Chem. 2020;16(2):202-211. doi: 10.2174/1573406415666190626130453. PMID: 31241438. 17: Szallasi A, Cruz F, Geppetti P. TRPV1: a therapeutic target for novel analgesic drugs? Trends Mol Med. 2006 Nov;12(11):545-54. doi: 10.1016/j.molmed.2006.09.001. Epub 2006 Sep 25. PMID: 16996800. 18: Karelia D, Corey Z, Wang H, Raup-Konsavage WM, Vrana KE, Lü J, Jiang C. Library Screening and Preliminary Characterization of Synthetic Cannabinoids Against Prostate and Pancreatic Cancer Cell Lines. Cannabis Cannabinoid Res. 2024 Apr;9(2):523-536. doi: 10.1089/can.2022.0270. Epub 2023 Mar 7. PMID: 36880938. 19: 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. PMID: 24666696. 20: Yang F, Zhou L, Wang D, Yang LL, Yuan GR, Huang QY. Suppression of TRPV4 channels ameliorates anti-dipsogenic effects under hypoxia in the subfornical organ of rats. Sci Rep. 2016 Jul 20;6:30168. doi: 10.1038/srep30168. PMID: 27436489; PMCID: PMC4951807.