Publications

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2016

A rational approach for the discovery of NSD2 inhibitors for the treatment of multiple myeloma
2nd Annual Epigenetics Discovery Congress, London, September 8-9
Xavier Espanel, Séverine Estevez, Vanessa Adarbes, Stéphanie Bocart, Bruno Loillier, Séverine Delaporte, Elina Mandry

IVA336 a Potential Substrate Reduction Therapy for Mucopolysaccharidose type-VI, -I, and -II Diseases
MPS 2016, Bonn, July 13-14
Mireille Tallandier ,Philippe Masson, Eugeni Entchev, Sebastien Jacquet, Ingrid Jantzen, Olivier Lacombe, Véronique Douet

A rational approach for the discovery of inhibitors of NSD2 for the treatment of cancer
AACR 2016, New Orleans, April 16-20
Claudia Fromond, Xavier Espanel, Séverine Estevez, Vanessa Adarbes, Stéphanie Bocart, Bruno Loillier

The pan-PPAR agonist IVA337 has anti-fibrotic effects in multiple in vitro and in vivo fibrosis models
4th Systemic Sclerosis World Congress, Lisbon, February 18-20
Irena Konstantinova, Jean-Michel Luccarini, Evelyne Defrêne, Céline Estivalet, Ingrid Jantzen, Julien Tessier.

2015

Discovery of YAP-TEAD Protein-Protein interaction (PPI) inhibitors for the treatment of cancer
AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boston, MA, November 5-9
Anne Soude, Martine Barth, Stéphanie Bocart, Frédéric Thoreau, Elina Mandry, Sylvie Contal

A Rational Approach for the Discovery of NSD2 Inhibitors for the Treatment of Cancer
Miptec 2015, Basel, Sept 19-23
13th annual Discovery On Target, Boston, MA, September 22-23
Xavier Espanel, Séverine Estevez, Vanessa Adarbes, Stéphanie Bocart, Bruno Loillier, and Christian Montalbetti

Inhibition of two NADPH-independent enzymatic activities: Aldehyde oxidase and Xanthine oxidase inhibition
18th International Conference on Drug-Drug Interactions ,Washington, June 29- July 1st
Didier Bressac, Rachel Dechaume, Aurélie Péraire, Emmanuel Hardillier, Christelle Gondran, Eric Lecocq, Olivier Lacombe

Rodent Pharmacokinetics and in vitro ADME Properties of IV3086: An orally available and brain penetrant NURR1/RXR Activator
ISSX - 13th European Meeting, Glasgow, June 22-25
Bruno Bournique, Didier Bressac, Emmanuel Hardillier, Olivier Lacombe

A rational approach for the discovery of inhibitors of the YAP-TEAD interaction
Drug Discovery Chemistry , San Diego , April 21-23
Christian Montalbetti, Claudia Fromond, Laurent Chene, Anne Soude, Martine Barth, Sylvie Contal and Pierre Broqua

Identification of G9a inhibitors by AlphaLisa™ technology and hit confirmation using MT-Glo™
AACR, Philadelphia, April 18-22
Claudia Fromond, Xavier Espanel, Laurent Chene, Philippe Masson, BenaïssaBoubia, Christian Montalbetti, Pierre Broqua

A rational approach for the discovery of inhibitors of NSD2 for the treatment of cancer
AACR, Philadelphia, April 18-22
Claudia Fromond, Xavier Espanel, Anne Soudé, Laurent Chene, Philippe Masson, BenaïssaBoubia, Christian Montalbetti and Pierre Broqua

A rational approach for discovery of inhibitors of YAP-TEAD interaction
AACR, Philadelphia, April 18-22 
Claudia Fromond, Laurent Chene, Anne Soude, Martine Barth, Christian Montalbetti and Pierre Broqua

Identification of G9a inhibitors by Alphalisa™ and hit confirmation using MT-Glo™
SLAS 2015, Washington DC, February 7-11.
Philippe Masson, Vanessa Adarbes, Stéphanie Bocart , Séverine Estevez , Bruno Loillier, Laurent Chêne, Christian Montalbetti, Claudia Fromond, Benaissa Boubia and Xavier Espanel.

Ultrafast LC-UV-ELSD-MS confirming the high quality of Inventiva's screening collection 
SLAS 2015, Washington DC, February 7-11.
Frédéric Bell, Clément Gaiffe, Amandine Vessot Jérôme Amaudrut, Sylvaine Marie, Philippe Masson.

A rational approach for the discovery of inhibitors of NSD2 for the treatment of cancer
Epigenetics and Cancer , Keystone Colorado , January 25-30.
Xavier Espanel, Séverine Estevez, Vanessa Adarbes, Stéphanie Bocart, Bruno Loillier, Séverine Delaporte, Elina Mandry, Anne Soudé, Laurent Chene, Philippe Masson, Benaïssa Boubia, Christian Montalbetti, Pierre Broqua and Claudia Fromond.

2014

Identification of novel EZH2 inhibitor scaffolds
26th EORTC-NCI-AACR symposium, Barcelona, Nov 18-21.
Xavier Espanel, Laurent Chene, Anne Soude, Séverine Estevez, Vanessa Adarbes, Bruno Loillier, Benaissa Boubia, Philippe Masson, Christian Montalbetti, Pierre Broqua & Claudia Z. A. Fromond.

A rational approach for discovery of inhibitors of YAP-TEAD interaction
26th EORTC-NCI-AACR symposium, Barcelona, Nov 18-21.
Laurent Chene, Anne Soude, Christelle Valaire, Severine Delaporte, Sebastien Jacquet, Yves Cambet, Isabelle Braccini, Martine Barth, Christian Montalbetti, Pierre Broqua & Claudia Z-A Fromond.

One Hour Pre-Infusion followed by Four Hours Co-Infusion of Elacridar as a Tool to Identify the Involvement of P-gp and BCRP in the Brain Penetration of Test Compounds in Rats
19th North American Congress of the International Society for the Study of Xenobiotics, San Francisco, Oct 19-23.
B. Bournique, B. Cautain, V. Douet, C. Eymann, C. Gondran, E. Hardillier, L. Nicolas, O. Lacombe.

A Useful Relationship between In Vivo Rat Kp Brain and In Vitro Caco-2 Cells Efflux Ratio
19th North American Congress of the International Society for the Study of Xenobiotics, San Francisco, Oct 19-23.
B. Bournique, JM. Bony, D.Bressac, B. Cautain, R.Dechaume, V. Douet, C. Eymann, C. Gondran, E.Hardillier, L. Nicolas, O. Lacombe.

Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit.

George DM, Breinlinger EC, Friedman M, Zhang Y, Wang J, Argiriadi M, Bansal-Pakala P, Barth M, Duignan DB, Honore P, Lang Q, Mittelstadt S, Potin D, Rundell L, Edmunds JJ.

Abstract

Protein kinase Cθ (PKCθ) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKCθ inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

J. Med. Chem., 2015, 58 (1), pp 222–236
DOI: 10.1021/jm500669m
Publication Date (Web): June 24, 2014

http://pubs.acs.org/doi/abs/10.1021/jm500669m

A Rapid LC-hrMS Method for Metabolite Identification Simultaneously to Metabolic Stability Assessment on Microsomes at an Early Screening Stage
International Mass Spectrometry,Geneve,August 24-29.
Emmanuel Hardillier, Didier Bressac, Olivier Lacombe

Discovery and optimization of indoline derivatives as new LXR agonists
248TH ACS National Meeting & Exposition, San Francisco, August 10-14.
Dominique Potin, Jérôme Amaudrut

Compound-oriented preparative HPLC purification platform
10th International  Symposium on Drug Analysis, Liège, June 23-25.
Nathalie Urban, Frédéric Bell, Cyrielle Couchoux

Solubility toolbox for successful design of drug candidates
10th International  Symposium on Drug Analysis, Liège, June 23-25.
Frédéric Bell, Caroline Durand, Nathalie Urban

In Vitro-In Vivo Correlation (IVIVC) for clearance estimation in earlyADME : the importance of unbound fraction assessment in plasma and microsomes
20th International Symposium on Microsomes and Drug Oxidations, Leinfelden, May 18-22.
Didier Bressac, Rachel Dechaume, Jeanne-Marie Bony, Olivier Lacombe

Screening Library Enrichment: Criteria that matter, timely manner
Openeye European User Meeting, Mery sur Oise, May 14-16.
Jérôme Amaudrut, Fabrice Guillier

Development and automation of a fibrotic phenotypic screening using a High Content Screening approach
Keystone Fibrosis, Keystone Colorado, March 23-28.
Laurent Chêne, Anne Soude, Philippe Masson and Xavier Espanel

Identification of novel EZH2 inhibitor scaffolds
Keystone Cancer Epigenetics, Santa Fé, February 4-9.
Xavier Espanel, Christian Montalbetti, Claudia Fromond

A Selective NURR1/RXR activation for treating Parkinson’s disease
Keystone Nuclear Receptors ,Taos , January 10-15.
B.Boubia, O. Lacombe, M. Tallandier

2013

Practical synthesis of N-substituted naphthyridine
18th European Symposium on Organic Chemistry, Marseille, July 7-12.
Laurent Mignon

Synthesis of substituted phenyl acetic acid and 5-membered heterocycles derivatives.
18th European Symposium on Organic Chemistry , Marseille, July 7-12.
L. Mounier, M. Barth, B. Boubia

Supporting the Reactivity Assessment of an IVA Acyl-Glucuronide Derivative
HPLC 2013, Amsterdam, June 16-20.
Emmanuel Hardillier, Béatrice Cautain, Olivier Lacombe

Interaction scanning libraries: A general strategy for scaffold functionalization
International Symposium on Advances in Synthetic and Medicinal Chemistry, Moscow,  May 5-8.
Fabrice Guillier, Jérôme Amaudrut, Jonathan Llacer, Jérôme Gonzalez