Literature DB >> 24283972

A unique industrial-academic collaboration towards the next generation of schizophrenia therapeutics.

Gregor J Macdonald, Craig W Lindsley1.   

Abstract

This article describes the unique industrial-academic collaboration that has been running for four years between Janssen Pharmaceutica NV and the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD) towards identifying the next generation of schizophrenia therapeutics. This was a true collaboration, with both entities engaged in chemistry, In vitro pharmacology, DMPK and In vivo behavioral pharmacology, and aligned to deliver a first-in-class clinical candidate (NME) and additional back-up molecules. Notably, a first NME was delivered in a rapid timeframe and targeted the novel mechanism of mGlu5 positive allosteric modulation. As with any true collaboration, both sides brought unique skills to the table--Janssen leveraged deep drug discovery expertise and infrastructure, while Vanderbilt brought deep knowledge of the chemistry and pharmacology of the target in addition to the ability to provide deep scientific insight into the mechanism behind target modulation. In this article, we will discuss the science which drove our collaboration as well as some key lessons learned.

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Year:  2014        PMID: 24283972     DOI: 10.2174/1568026613666131127154443

Source DB:  PubMed          Journal:  Curr Top Med Chem        ISSN: 1568-0266            Impact factor:   3.295


  7 in total

1.  Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia.

Authors:  Susana Conde-Ceide; Carlos M Martínez-Viturro; Jesús Alcázar; Pedro M Garcia-Barrantes; Hilde Lavreysen; Claire Mackie; Paige N Vinson; Jerri M Rook; Thomas M Bridges; J Scott Daniels; Anton Megens; Xavier Langlois; Wilhelmus H Drinkenburg; Abdellah Ahnaou; Colleen M Niswender; Carrie K Jones; Gregor J Macdonald; Thomas Steckler; P Jeffrey Conn; Shaun R Stauffer; José Manuel Bartolomé-Nebreda; Craig W Lindsley
Journal:  ACS Med Chem Lett       Date:  2015-05-20       Impact factor: 4.345

Review 2.  Computational Advances for the Development of Allosteric Modulators and Bitopic Ligands in G Protein-Coupled Receptors.

Authors:  Zhiwei Feng; Guanxing Hu; Shifan Ma; Xiang-Qun Xie
Journal:  AAPS J       Date:  2015-05-05       Impact factor: 4.009

3.  Allosteric Binding Site and Activation Mechanism of Class C G-Protein Coupled Receptors: Metabotropic Glutamate Receptor Family.

Authors:  Zhiwei Feng; Shifan Ma; Guanxing Hu; Xiang-Qun Xie
Journal:  AAPS J       Date:  2015-03-12       Impact factor: 4.009

4.  Further optimization of the mGlu5 PAM clinical candidate VU0409551/JNJ-46778212: Progress and challenges towards a back-up compound.

Authors:  Ya Zhou; Chrysa Malosh; Susana Conde-Ceide; Carlos Manuel Martínez-Viturro; Jesus Alcázar; Hilde Lavreysen; Claire Mackie; Thomas M Bridges; J Scott Daniels; Colleen M Niswender; Carrie K Jones; Gregor J Macdonald; Thomas Steckler; P Jeffrey Conn; Shaun R Stauffer; José Manuel Bartolomé-Nebreda; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2015-07-04       Impact factor: 2.823

Review 5.  Mitigating risk in academic preclinical drug discovery.

Authors:  Jayme L Dahlin; James Inglese; Michael A Walters
Journal:  Nat Rev Drug Discov       Date:  2015-04       Impact factor: 84.694

6.  Preliminary investigation of 6,7-dihydropyrazolo[1,5-a]pyrazin-4-one derivatives as a novel series of mGlu5 receptor positive allosteric modulators with efficacy in preclinical models of schizophrenia.

Authors:  Susana Conde-Ceide; Jesús Alcázar; Sergio A Alonso de Diego; Silvia López; María Luz Martín-Martín; Carlos M Martínez-Viturro; Miguel-Angel Pena; Han Min Tong; Hilde Lavreysen; Claire Mackie; Thomas M Bridges; J Scott Daniels; Colleen M Niswender; Carrie K Jones; Gregor J Macdonald; Thomas Steckler; P Jeffrey Conn; Shaun R Stauffer; Craig W Lindsley; José Manuel Bartolomé-Nebreda
Journal:  Bioorg Med Chem Lett       Date:  2015-11-28       Impact factor: 2.823

Review 7.  Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders.

Authors:  P Jeffrey Conn; Craig W Lindsley; Jens Meiler; Colleen M Niswender
Journal:  Nat Rev Drug Discov       Date:  2014-09       Impact factor: 84.694

  7 in total

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