Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain
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 ef...
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| Veröffentlicht in: | ACS medicinal chemistry letters 2017-12, Vol.8 (12), p.1309-1313 |
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| container_title | ACS medicinal chemistry letters |
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| creator | Han, Sangdon Thoresen, Lars Jung, Jae-Kyu Zhu, Xiuwen Thatte, Jayant Solomon, Michelle Gaidarov, Ibragim Unett, David J Yoon, Woo Hyun Barden, Jeremy Sadeque, Abu Usmani, Amin Chen, Chuan Semple, Graeme Grottick, Andrew J Al-Shamma, Hussein Christopher, Ronald Jones, Robert M |
| description | 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. |
| doi_str_mv | 10.1021/acsmedchemlett.7b00396 |
| format | Article |
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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. 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Chem. Lett</addtitle><description>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. 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Chem. Lett</addtitle><date>2017-12-14</date><risdate>2017</risdate><volume>8</volume><issue>12</issue><spage>1309</spage><epage>1313</epage><pages>1309-1313</pages><issn>1948-5875</issn><eissn>1948-5875</eissn><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.</abstract><pub>American Chemical Society</pub><pmid>29259753</pmid><doi>10.1021/acsmedchemlett.7b00396</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-9666-1588</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1948-5875 |
| ispartof | ACS medicinal chemistry letters, 2017-12, Vol.8 (12), p.1309-1313 |
| issn | 1948-5875 1948-5875 |
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| source | ACS Publications; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Letter |
| title | Discovery of APD371: Identification of a Highly Potent and Selective CB2 Agonist for the Treatment of Chronic Pain |
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