AMG-517

AMG 517 is a potent and selective TRPV1 antagonist, antagonizes capsaicin, proton, and heat activation of TRPV1 with IC50 of 0.76 nM, 0.62 nM and 1.3 nM. (In Vitro) :AMG 517 retains potency in the capsaicin- and acid-mediated assays with IC50 values of 0.9 and 0.5 nM. AMG 517 inhibits capsaicin, pH 5, and heat-induced45Ca2+ uptake into cells expressing TRPV1 with IC50 values of 1 to 2 nM. AMG 517 blocks capsaicin-, proton-, and heat-induced inward currents in TRPV1-expressing cells similarly. AMG 517 inhibits native TRPV1 activation by capsaicin in rat dorsal root ganglion neurons with an IC50 value of 0.68 ± 0.2 nM. AMG 517 is a competitive antagonist of both rat and human TRPV1 with dissociation constant (Kb) values of 4.2 and 6.2 nM, respectively. (In Vivo) :AMG 517 is shown to be effective in a rodent “on-target” biochemical challenge model (capsaicin-induced flinch, ED50=0.33 mg/kg p.o.) and is antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED=0.83 mg/kg, p.o.) .The minimally effective dose is 0.3 mg/kg for AMG 517 and the corresponding plasma concentration is 90 ng/mL. Oral administration of AMG 517 reverses established thermal hyperalgesia in a dose-dependent manner at 21 h after CFA injection. AMG 517 causes transient hyperthermia in rodents, dogs, and monkeys. AMG 517 induces hyperthermia in a steep dose-dependent manner, with 0.3, 1, and 3 mg/kg associated with 0.5, 0.6, and 1.6°C increases in body temperature, respectively. Body temperatures of rats treated with all doses of AMG 517 return to baseline within 10 to 20 h.

659730-32-2

AMG-517 | AMG 517 | AMG517 | BD-0082

>98% (HPLC)

DMSO:86 mg/mL (199.81 mM) Ethanol:<1 mg/mL (<1 mM) Water:<1 mg/mL (<1 mM)

CC (NC1=NC2=C (OC3=NC=NC (C4=CC=C (C (F) (F) F) C=C4) =C3) C=CC=C2S1) =O

C20H13F3N4O2S

430.4

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.