SB705498, ≥99%
Product Name： SB705498
別名:(R)-1-(2-bromophenyl)-3-(1-(5-(trifluoromethyl)pyridin-2-yl)pyrrolidin-3-yl)urea
CAS號:501951-42-4
分子式:C17H16BrF3N4O
分子量:429.23
貯存： 儲存溫度-20°C
可溶性：
DMSO 86 mg/mL
Water <1 mg/mL
Ethanol 20 mg/mL
生化和生理學(xué)機(jī)理：
SB-705498 is a potent, selective and orally bioavailable transient receptor potential vanilloid 1 (TRPV1) receptor antagonist with a pIC50 of 7.1. SB-705498 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 SB-705498 rapidly, completely and reversibly inhibits hTRPV1 expressed in HEK293 cells. Compared with placebo, SB-705498 reduced the area of capsaicin-evoked flare (P=0.0047). The heat pain threshold on non-sensitised skin was elevated following SB-705498 (estimated difference from placebo [95% confidence intervals]： 1.3 degrees C [0.07,2.53], P=0.019). Following capsaicin sensitisation, the heat pain threshold and tolerance were similar between SB-705498 and placebo. However, SB-705498 increased heat pain tolerance at the site of UVB-evoked inflammation (estimated difference from placebo： 0.93 degrees C [0.25,1.6], P=0.0054). The magnitude of the pharmacodynamic effects of SB-705498 appeared to be related to plasma concentration. These results indicate that SB-705498, at a clinically safe and well-tolerated dose, has target-specific pharmacodynamic activity in humans. These data provide the first clinical evidence that a TRPV1 antagonist may alleviate pain and hyperalgesia associated with inflammation and tissue injury.
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