2. Academic Validation
  3. Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain

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. doi: 10.1021/acsmedchemlett.7b00396.
Sangdon Han 1,  Lars Thoresen 1,  Jae-Kyu Jung 1,  Xiuwen Zhu 1,  Jayant Thatte 1,  Michelle Solomon 1,  Ibragim Gaidarov 1,  David J Unett 1,  Woo Hyun Yoon 1,  Jeremy Barden 1,  Abu Sadeque 1,  Amin Usmani 1,  Chuan Chen 1,  Graeme Semple 1,  Andrew J Grottick 1,  Hussein Al-Shamma 1,  Ronald Christopher 1,  Robert M Jones 1
Affiliations

Affiliation

  • 1 Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, California 92121, United States.
PMID: 29259753 DOI: 10.1021/acsmedchemlett.7b00396
Abstract

The discovery of a novel, selective and fully efficacious CB2 agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound 6 was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB2 receptor to avoid tachyphylaxis. Based on its overall favorable preclinical profile, 6 (APD371) was selected for further development for the treatment of pain.

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