501951-42-4 Usage
Description
SB-705498 is an orally bioavailable, competitive antagonist specifically designed to inhibit the activation of transient receptor potential vanilloid type 1 (TRPV1) receptors. These receptors are nonselective cation channels that can be gated by noxious heat, protons, and capsaicin. SB-705498 effectively blocks capsaicin-mediated activation of TRPV1 receptors in humans, rats, and guinea pigs, with high affinity (pKis of 7.6, 7.5, and 7.3, respectively). It rapidly and reversibly inhibits the activation of human TRPV1 by capsaicin (IC50 = 3 nM), acid (pH 5.3), or heat (50°C; IC50 = 6 nM) at a voltage of -70 mV.
Uses
Used in Pharmaceutical Industry:
SB-705498 is used as a therapeutic agent for the treatment of pain and inflammation. Its ability to inhibit the TRPV1 receptors, which are involved in sensing pain and temperature, makes it a potential candidate for managing conditions characterized by thermal hyperalgesia and inflammatory pain.
Used in Research Applications:
SB-705498 is used as a research tool for studying the role of TRPV1 receptors in various physiological and pathological processes. It can help researchers understand the molecular mechanisms underlying pain sensation, temperature regulation, and other related functions.
Used in Drug Development:
SB-705498 serves as a lead compound in the development of new drugs targeting TRPV1 receptors. Its high selectivity and potency make it a valuable starting point for designing more effective and safer medications for pain management and other TRPV1-related conditions.
Used in Neurological Applications:
SB-705498 is used as a neuromodulatory agent for the investigation of TRPV1 receptor function in the nervous system. It can be employed to study the role of these receptors in neuropathic pain, migraine, and other neurological disorders associated with altered sensory processing.
in vitro
using a ca2+-based fluorometric imaging plate reader (flipr) assay, sb-705498 was shown to be a potent competitive antagonist of the capsaicin-mediated activation of the human trpv1 receptor (pki = 7.6) with activity at rat (pki = 7.5) and guinea pig (pki = 7.3) orthologs. sb-705498 caused rapid and reversible inhibition of the capsaicin (ic50 = 3 nm)-, acid (ph 5.3)-, or heat (50°c; ic50 = 6 nm)-mediated activation of human trpv1 (at =70 mv) [1].
in vivo
having initially demonstrated that sb-705498 showed good overall in vitro efficacy and oral bioavailability in rat, the in vivo activity of sb-705498 was investigated in the capsaicin-induced secondary hyperalgesia model9 in the rat. this model demonstrates the compound’s antagonist activity in vivo against the specific trpv1 agonist capsaicin. as an early indicator of potential pharmacodynamic activity, sb-705498 showed excellent activity at 10 and 30 mg/kg po with good reversal of allodynia. furthermore, sb-705498 was also shown to give 80% reversal of allodynia in the guinea pig fca model at 10 mg/kg po [2].
References
Rami et al. (2006), ?Discovery of SB-705498: a potent and orally bioavailable TRPV1 antagonist suitable for clinical development; Bioorg. Med. Chem. Lett., 16 3287
Gunthorpe et al. (2007), 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., 321 1183
Check Digit Verification of cas no
The CAS Registry Mumber 501951-42-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,0,1,9,5 and 1 respectively; the second part has 2 digits, 4 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 501951-42:
(8*5)+(7*0)+(6*1)+(5*9)+(4*5)+(3*1)+(2*4)+(1*2)=124
124 % 10 = 4
So 501951-42-4 is a valid CAS Registry Number.
501951-42-4Relevant articles and documents
Discovery of SB-705498: A potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development
Rami, Harshad K.,Thompson, Mervyn,Stemp, Geoffrey,Fell, Steve,Jerman, Jeffrey C.,Stevens, Alexander J.,Smart, Darren,Sargent, Becky,Sanderson, Dominic,Randall, Andrew D.,Gunthorpe, Martin J.,Davis, John B.
, p. 3287 - 3291 (2007/10/03)
Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat). Furthermore, 15 possessed suitable developability properties to enable progression of this compound into in vivo studies and subsequently clinical development.
