LY2828360 是一种作用缓慢的、有效的 G 蛋白偏倚的大麻素受体 2(CB2)激动剂，能够抑制 cAMP 的积累并激活 ERK1/2 通路。

LY2828360 is a cannabinoid (CB) receptor 2 agonist (Ki = 40.3 nM). It selectively activates CB2 over CB1 in a GTPγS binding assay (EC50s = 20.1 and >100,000 nM, respectively).

In vitro, LY2828360 was a slowly acting but efficacious G protein-biased CB2 agonist, inhibiting cAMP accumulation and activating extracellular signal-regulated kinase 1/2 signaling while failing to recruit arrestin, activate inositol phosphate signaling, or internalize CB2 receptors.

In wild-type (WT) mice, LY2828360 (3 mg/kg per day × 12 days) suppressed chemotherapy-induced neuropathic pain produced by paclitaxel without producing tolerance. Antiallodynic efficacy of LY2828360 was absent in CB2 knockout (KO) mice. Morphine (10 mg/kg per day × 12 days) tolerance developed in CB2KO mice but not in WT mice with a history of LY2828360 treatment (3 mg/kg per day × 12 days). LY2828360-induced antiallodynic efficacy was preserved in WT mice previously rendered tolerant to morphine (10 mg/kg per day × 12 days), but it was absent in morphine-tolerant CB2KO mice. Coadministration of LY2828360 (0.1 mg/kg per day × 12 days) with morphine (10 mg/kg per day × 12 days) blocked morphine tolerance in WT but not in CB2KO mice. WT mice that received LY2828360 coadministered with morphine exhibited a trend (P = 0.055) toward fewer naloxone-precipitated jumps compared with CB2KO mice. LY2828360 is a slowly signaling, G protein-biased CB2 agonist that attenuates chemotherapy-induced neuropathic pain without producing tolerance and may prolong effective opioid analgesia while reducing opioid dependence. LY2828360 may be useful as a first-line treatment in chemotherapy-induced neuropathic pain and may be highly efficacious in neuropathic pain states that are refractive to opioid analgesics.

1231220-79-3

C22H27ClN6O

426.95

DMSO:20.83 mg/mL (48.79 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years