Literature DB >> 20140821

Tanezumab, a recombinant humanized mAb against nerve growth factor for the treatment of acute and chronic pain.

Antonino Cattaneo1.   

Abstract

Persistent pain represents a major health problem, and most current therapeutic approaches are associated with unwanted effects and unsatisfactory pain relief. Therefore, an urgent need exists to develop more effective drugs that are directed toward new molecular targets. Nerve growth factor (NGF) is involved in pain transduction mechanisms, playing a key role as a master switch in many chronic and inflammatory pain states; the NGF ligand and its receptor TrkA constitute well-validated targets for pain therapy. Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions. In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models. Phase I and II clinical trials in osteoarthritic pain and chronic lower back pain demonstrated good efficacy for the compound, as well as a good safety and tolerability profile. Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system.

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Year:  2010        PMID: 20140821

Source DB:  PubMed          Journal:  Curr Opin Mol Ther        ISSN: 1464-8431


  38 in total

Review 1.  The discovery and development of analgesics: new mechanisms, new modalities.

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Journal:  J Clin Invest       Date:  2010-11-01       Impact factor: 14.808

2.  The fundamental unit of pain is the cell.

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3.  A fully caninised anti-NGF monoclonal antibody for pain relief in dogs.

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4.  Persistent Nociception Triggered by Nerve Growth Factor (NGF) Is Mediated by TRPV1 and Oxidative Mechanisms.

Authors:  Michael A Eskander; Shivani Ruparel; Dustin P Green; Paul B Chen; Elaine D Por; Nathaniel A Jeske; Xiaoli Gao; Eric R Flores; Kenneth M Hargreaves
Journal:  J Neurosci       Date:  2015-06-03       Impact factor: 6.167

Review 5.  Growth factors and neuropathic pain.

Authors:  Michael H Ossipov
Journal:  Curr Pain Headache Rep       Date:  2011-06

6.  Potential mechanisms for hypoalgesia induced by anti-nerve growth factor immunoglobulin are identified using autoimmune nerve growth factor deprivation.

Authors:  E M Hoffman; Z Zhang; M B Anderson; R Schechter; K E Miller
Journal:  Neuroscience       Date:  2011-07-28       Impact factor: 3.590

Review 7.  Cells and cell lysates: a direct approach for engineering antibodies against membrane proteins using yeast surface display.

Authors:  Benjamin J Tillotson; Yong Ku Cho; Eric V Shusta
Journal:  Methods       Date:  2012-03-23       Impact factor: 3.608

Review 8.  Predictive validity of behavioural animal models for chronic pain.

Authors:  Odd-Geir Berge
Journal:  Br J Pharmacol       Date:  2011-10       Impact factor: 8.739

9.  The TrkA receptor mediates experimental thermal hyperalgesia produced by nerve growth factor: Modulation by the p75 neurotrophin receptor.

Authors:  Alla Khodorova; Grant D Nicol; Gary Strichartz
Journal:  Neuroscience       Date:  2016-11-05       Impact factor: 3.590

10.  Systems pharmacology of the nerve growth factor pathway: use of a systems biology model for the identification of key drug targets using sensitivity analysis and the integration of physiology and pharmacology.

Authors:  Neil Benson; Tomomi Matsuura; Sergey Smirnov; Oleg Demin; Hannah M Jones; Pinky Dua; Piet H van der Graaf
Journal:  Interface Focus       Date:  2013-04-06       Impact factor: 3.906

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