Literature DB >> 29259753

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

Sangdon Han1, Lars Thoresen1, Jae-Kyu Jung1, Xiuwen Zhu1, Jayant Thatte1, Michelle Solomon1, Ibragim Gaidarov1, David J Unett1, Woo Hyun Yoon1, Jeremy Barden1, Abu Sadeque1, Amin Usmani1, Chuan Chen1, Graeme Semple1, Andrew J Grottick1, Hussein Al-Shamma1, Ronald Christopher1, Robert M Jones1.   

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.

Entities:  

Year:  2017        PMID： 29259753      PMCID： PMC5733264          DOI： 10.1021/acsmedchemlett.7b00396

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  23 in total

1.  CB2 cannabinoid receptor-mediated peripheral antinociception.

Authors:  T P Malan; M M Ibrahim; H Deng; Q Liu; H P Mata; T Vanderah; F Porreca; A Makriyannis
Journal:  Pain       Date:  2001-09       Impact factor: 6.961

2.  Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists.

Authors:  Sangdon Han; Lars Thoresen; Xiuwen Zhu; Sanju Narayanan; Jae-Kyu Jung; Sonja Strah-Pleynet; Marc Decaire; Karoline Choi; Yifeng Xiong; Dawei Yue; Graeme Semple; Jayant Thatte; Michelle Solomon; Lixia Fu; Kevin Whelan; Hussien Al-Shamma; Joel Gatlin; Ruoping Chen; Huong Dang; Cameron Pride; Ibragim Gaidarov; David J Unett; Dominic P Behan; Abu Sadeque; Khawja A Usmani; Chuan Chen; Jeffrey Edwards; Michael Morgan; Robert M Jones
Journal:  Bioorg Med Chem Lett       Date:  2014-11-26       Impact factor: 2.823

Review 3.  Emerging drugs for neuropathic pain.

Authors:  Ian Gilron; Anthony H Dickenson
Journal:  Expert Opin Emerg Drugs       Date:  2014-05-03       Impact factor: 4.191

Review 4.  Cannabinoids as novel anti-inflammatory drugs.

Authors:  Prakash Nagarkatti; Rupal Pandey; Sadiye Amcaoglu Rieder; Venkatesh L Hegde; Mitzi Nagarkatti
Journal:  Future Med Chem       Date:  2009-10       Impact factor: 3.808

5.  Molecular characterization of a peripheral receptor for cannabinoids.

Authors:  S Munro; K L Thomas; M Abu-Shaar
Journal:  Nature       Date:  1993-09-02       Impact factor: 49.962

6.  Delta 9-tetrahydrocannabinol inhibits electrically-evoked CGRP release and capsaicin-sensitive sensory neurogenic vasodilatation in the rat mesenteric arterial bed.

Authors:  J D Wilkinson; D A Kendall; V Ralevic
Journal:  Br J Pharmacol       Date:  2007-09-10       Impact factor: 8.739

7.  Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons.

Authors:  Uma Anand; William R Otto; Daniel Sanchez-Herrera; Paul Facer; Yiangos Yiangou; Yuri Korchev; Rolfe Birch; Christopher Benham; Chas Bountra; Iain P Chessell; Praveen Anand
Journal:  Pain       Date:  2008-08-09       Impact factor: 6.961

8.  Inhibition of inflammatory hyperalgesia by activation of peripheral CB2 cannabinoid receptors.

Authors:  Aline Quartilho; Heriberto P Mata; Mohab M Ibrahim; Todd W Vanderah; Frank Porreca; Alexandros Makriyannis; T Philip Malan
Journal:  Anesthesiology       Date:  2003-10       Impact factor: 7.892

9.  Cannabinoid receptor localization in brain.

Authors:  M Herkenham; A B Lynn; M D Little; M R Johnson; L S Melvin; B R de Costa; K C Rice
Journal:  Proc Natl Acad Sci U S A       Date:  1990-03       Impact factor: 11.205

10.  Selective activation of cannabinoid CB(2) receptors suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.

Authors:  A G Nackley; A Makriyannis; A G Hohmann
Journal:  Neuroscience       Date:  2003       Impact factor: 3.590
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  6 in total

Review 1.  Druggable targets of the endocannabinoid system: Implications for the treatment of HIV-associated neurocognitive disorder.

Authors:  Mariah M Wu; Xinwen Zhang; Melissa J Asher; Stanley A Thayer
Journal:  Brain Res       Date:  2019-09-17       Impact factor: 3.252

Review 2.  AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review.

Authors:  Jean-Frederic Colombel; Andrea Shin; Peter R Gibson
Journal:  Clin Gastroenterol Hepatol       Date:  2018-08-09       Impact factor: 11.382

3.  Activating cannabinoid receptor 2 preserves axonal health through GSK-3β/NRF2 axis in adrenoleukodystrophy.

Authors:  Janani Parameswaran; Leire Goicoechea; Laura Planas-Serra; Antoni Pastor; Montserrat Ruiz; Noel Y Calingasan; Cristina Guilera; Ester Aso; Jordi Boada; Reinald Pamplona; Manuel Portero-Otín; Rafael de la Torre; Isidre Ferrer; Carlos Casasnovas; Aurora Pujol; Stéphane Fourcade
Journal:  Acta Neuropathol       Date:  2022-07-01       Impact factor: 15.887

4.  Classification models and SAR analysis on CysLT1 receptor antagonists using machine learning algorithms.

Authors:  Hongzhao Wang; Zijian Qin; Aixia Yan
Journal:  Mol Divers       Date:  2021-02-03       Impact factor: 3.364

Review 5.  Gastrointestinal pain.

Authors:  Asbjørn M Drewes; Anne E Olesen; Adam D Farmer; Eva Szigethy; Vinciane Rebours; Søren S Olesen
Journal:  Nat Rev Dis Primers       Date:  2020-01-06       Impact factor: 52.329

6.  Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents.

Authors:  Joel Castro; Sonia Garcia-Caraballo; Jessica Maddern; Gudrun Schober; Amanda Lumsden; Andrea Harrington; Shirdi Schmiel; Beatriz Lindstrom; John Adams; Stuart M Brierley
Journal:  Pain       Date:  2022-01-01       Impact factor: 6.961
  6 in total

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