Olorinab (APD 371) (APD 371) 是一种高效、选择性和完全有效的 2 型大麻素受体 (CB2) 激动剂，对 hCB2 的 EC50 为 6.2 nM。
Olorinab (APD 371) is a highly potent, selective and fully efficacious cannabinoid receptor type 2 (CB2) agonist, with an EC50 of 6.2 nM for hCB2.
A comprehensive in vitro profile of Olorinab (APD 371) (6) shows that single digit nanomolar potency and full intrinsic efficacy are maintained in all species assessed, and that Olorinab (APD 371) is highly selective for CB2 over CB1 in both binding and functional assays. Furthermore, Olorinab (APD 371) induces efficient receptor internalization (~106% relative to the CB1/2 agonist CP55,940) in CHO cells expressing HA-tagged rat CB2 suggesting that, according to the hypothesis, Olorinab (APD 371) would be able to drive agonist-induced receptor recycling[1].
Olorinab (APD 371) significantly increases paw withdrawal thresholds at doses ≥3 mg/kg PO (ED50=2.3 mg/kg). In a separate experiment, a single dose of Olorinab (APD 371) (10 mg/kg, PO) inhibits paw withdrawal threshold for up to 4 hours after administration. Seperately, the analgesic effects of Olorinab (APD 371) are shown to be highly likely mediated via activity at CB2 receptors[1].
[1]. Han S, et al. Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain. ACS Med Chem Lett. 2017 Nov 30;8(12):1309-1313.
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