Home Transmembrane Transporters TRP Channel antagonist SB705498

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SB705498 TRP Channel antagonist

Cat.No.S2773

SB705498 is a TRPV1 antagonist for hTRPV1, antagonizes capsaicin, acid, and heat activation of TRPV1 with IC50 of 3 nM, 0.1 nM and 6 nM, shows a degree of voltage dependence, exhibits >100-fold selectivity for TRPV1 over TRPM8. Phase 2.
SB705498 TRP Channel antagonist Chemical Structure

Chemical Structure

Molecular Weight: 429.23

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Quality Control

Batch: S277301 DMSO]86 mg/mL]false]Ethanol]20 mg/mL]false]Water]Insoluble]false Purity: 99.90%
99.90

Chemical Information, Storage & Stability

Molecular Weight 429.23 Formula

C17H16BrF3N4O

 Storage (From the date of receipt)
CAS No. 501951-42-4 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1CN(CC1NC(=O)NC2=CC=CC=C2Br)C3=NC=C(C=C3)C(F)(F)F

Solubility

In vitro
Batch:

DMSO : 86 mg/mL (200.35 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 20 mg/mL

Water : Insoluble

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Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
hTRPV1 [1]
7.6(pKi)
hTRPV1 [1]
7.1(pIC50)
In vitro
SB705498 (0.3 nM-1 μM) potently inhibits capsaicin-induced activation of human TRPV1 expressed in 1321N1 cells or HEK293 cells with apparent pKi of 7.5 or 7.6, respectively. Coapplication of 100 nM this compound rapidly, completely and reversibly inhibits hTRPV1 expressed in HEK293 cells. This chemical has no significant effect on endogenous [Ca2+] responses in HEK293 cells produced by muscarinic acetylcholine receptor activation with carbachol or store-operated channel-mediated Ca2+ entry after depletion of intracellular stores with the Ca2+ pump inhibitor thapsigargin. This compound (10 pM-1 μM) also has no significant antagonist effect versus the close TRPV1 receptor paralog TRPV4 transiently expressed in HEK293 cells and activated using the synthetic ligand 4α-phorbol-12,13-didecanoate (10 μM). This chemical reveals good antagonist potency against both the rat and guinea pig TRPV1. It antagonizes rat and guinea pig TRPV1 with pKi of 7.5 and 7.3, respectively. Coapplication of 100 nM to 10 μM this compound to the steady state of a maintained capsaicin response leads to rapid and complete inhibition of hTRPV1 at -70 mV. It inhibits capsaicin-mediated activation of hTRPV1 with IC50 of 3 nM and 17 nM at positive and negative holding potentials (-70 mV and + 70 mV), respectively. Coapplication of 1 μM this chemical to the plateau period of the response produces complete and reversible inhibition of the TRPV1-mediated conductance. [1] This compound shows approximately equal activity versus multiple and diverse chemical and physical modes of TRPV1 receptor activation. It shows little or no activity versus a wide range of ion channels, receptors and enzymes. This chemical produces full blockade of heat as well as pH activation of hTRPV1. [2]
In vivo
SB705498 exhibits potent and reversible blockade against the multiple modes of TRPV1 activation, namely the vanilloid (capsaicin), heat- and acid-mediated activation of the receptor. This compound displays excellent activity at 10 and 30 mg/kg po with good reversal of allodynia. It is also shown to give 80% reversal of allodynia in the guinea pig FCA model at 10 mg/kg p.o.. [2]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01476098 Completed
Rhinitis
GlaxoSmithKline
 April 2011 Phase 2
NCT01424397 Completed
Rhinitis
GlaxoSmithKline
 April 14 2011 Phase 2
NCT01424514 Completed
Rhinitis
GlaxoSmithKline
 December 1 2010 Phase 2
NCT01439308 Completed
Rhinitis
GlaxoSmithKline
 December 2009 Phase 2
NCT00461682 Terminated
Irritable Colon
GlaxoSmithKline
 January 26 2007 Phase 2

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