In silico design of low molecular weight protein-protein interaction inhibitors: Overall concept and recent advances

Progress in Biophysics and Molecular Biology
Mélaine A KuenemannBruno O Villoutreix

Abstract

Protein-protein interactions (PPIs) are carrying out diverse functions in living systems and are playing a major role in the health and disease states. Low molecular weight (LMW) "drug-like" inhibitors of PPIs would be very valuable not only to enhance our understanding over physiological processes but also for drug discovery endeavors. However, PPIs were deemed intractable by LMW chemicals during many years. But today, with the new experimental and in silico technologies that have been developed, about 50 PPIs have already been inhibited by LMW molecules. Here, we first focus on general concepts about protein-protein interactions, present a consensual view about ligandable pockets at the protein interfaces and the possibilities of using fast and cost effective structure-based virtual screening methods to identify PPI hits. We then discuss the design of compound collections dedicated to PPIs. Recent financial analyses of the field suggest that LMW PPI modulators could be gaining momentum over biologics in the coming years supporting further research in this area.

References

Jan 20, 1995·Science·T Clackson, J A Wells
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G CrucianiW Guba
Nov 5, 2002·Nature Reviews. Drug Discovery·Jürgen Bajorath
Apr 3, 2004·Nature Reviews. Drug Discovery·Michelle R Arkin, James A Wells
Jul 23, 2004·Proceedings of the National Academy of Sciences of the United States of America·Deepa RajamaniCarlos J Camacho
Aug 4, 2004·Current Opinion in Chemical Biology·Len PagliaroSteven Butcher
Dec 17, 2004·Nature·Brian K Shoichet
Feb 11, 2005·Bioinformatics·Alasdair T R Laurie, Richard M Jackson
Apr 2, 2005·Journal of Medicinal Chemistry·Philip J HajdukStephen W Fesik
Dec 27, 2005·Drug Discovery Today·Philip J HajdukChristin Tse
Jan 27, 2006·Proteins·Ludovic AutinBruno O Villoutreix
Jul 11, 2006·Current Opinion in Chemical Biology·John W DaviesJeremy L Jenkins
Aug 8, 2006·ChemMedChem·Scott P Brown, Philip J Hajduk
Sep 26, 2006·Drug Discovery Today·Christian N ParkerJürgen Bajorath
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Christopher D ThanosJames A Wells
Dec 13, 2006·Nature Reviews. Drug Discovery·David J PayneDavid L Pompliano
Jan 19, 2007·Chemico-biological Interactions·I M Kapetanovic
Feb 6, 2007·Bioinformatics·José Ignacio GarzónPablo Chacón
Jun 6, 2007·British Journal of Pharmacology·S EkinsB Testa
Jul 3, 2007·Journal of Medicinal Chemistry·Susanne Eyrisch, Volkhard Helms
Aug 19, 2007·Current Protein & Peptide Science·Bruno O VilloutreixMaria A Miteva
Aug 21, 2007·Journal of Medicinal Chemistry·Alexander NeugebauerChristian D Klein
Oct 16, 2007·Current Opinion in Chemical Biology·Campbell McInnes
Oct 24, 2007·Journal of Structural Biology·Yeturu Kalidas, Nagasuma Chandra
Feb 1, 2008·Journal of Medicinal Chemistry·M Paul Gleeson
Feb 28, 2008·Current Opinion in Structural Biology·Maxim Totrov, Ruben Abagyan
Apr 9, 2008·Current Pharmaceutical Biotechnology·Bruno O VilloutreixMaria A Miteva
Jun 10, 2008·The Journal of Allergy and Clinical Immunology·Elsa MazucPiona Dariavach
Aug 12, 2008·Bioorganic & Medicinal Chemistry Letters·Jason D HughesYao Zhang
Sep 25, 2008·Quarterly Reviews of Biophysics·Joël JaninPinak Chakrabarti
Dec 2, 2008·Drug Discovery Today·Jonathan C FullerRichard M Jackson
Jan 20, 2009·Drug Discovery Today·Simon Cross, Gabriele Cruciani
Apr 29, 2009·Nucleic Acids Research·Marylens HernandezRoberto Sanchez
May 9, 2009·Drug Discovery Today·Claudio N Cavasotto, Sharangdhar S Phatak
Jun 3, 2009·BMC Bioinformatics·Vincent Le GuillouxPierre Tuffery
Oct 9, 2009·Chemical Biology & Drug Design·Alícia P HiguerueloTom L Blundell
Oct 16, 2009·Journal of Medicinal Chemistry·Frank LoveringChristine Humblet
Oct 23, 2009·Journal of Chemical Information and Modeling·Hao FanAndrej Sali
Nov 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Tomasz Wlodarski, Bojan Zagrovic
Dec 9, 2009·Drug Discovery Today·Olivier SperandioBruno O Villoutreix
Dec 17, 2009·Journal of Chemical Information and Modeling·Manuel RuedaRuben Abagyan
Jan 20, 2010·Current Opinion in Structural Biology·Bruno O Villoutreix, Olivier Sperandio
Feb 20, 2010·Current Medicinal Chemistry·Simon LeisMartin Zacharias

❮ Previous
Next ❯

Citations

Oct 4, 2015·Nucleic Acids Research·Céline M LabbéOlivier Sperandio
Jun 26, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rushikesh Sable, Seetharama Jois
Dec 18, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ioanna PettaKarolien De Bosscher
Jan 5, 2016·Journal of Chemical Information and Modeling·David K Johnson, John Karanicolas
Mar 17, 2016·Database : the Journal of Biological Databases and Curation·Marie-Jeanne BassePhilippe Roche
Oct 13, 2015·Current Opinion in Microbiology·Bart L StakerPeter J Myler
Aug 9, 2015·Biochemical Pharmacology·Shyam Sunder Chatterjee
Sep 23, 2016·Future Medicinal Chemistry·Giovanna Zinzalla
Mar 12, 2016·Scientific Reports·Grégory MenchonPatrick Calsou
Jan 11, 2019·Organic & Biomolecular Chemistry·Jaru TaechalertpaisarnKevin Burgess
May 30, 2019·Future Medicinal Chemistry·Kanin WichapongGerry Af Nicolaes
Jul 13, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Wiktoria JedwabnyEdyta Dyguda-Kazimierowicz
Mar 10, 2018·Computer Graphics Forum : Journal of the European Association for Computer Graphics·Tiago SimõesAbel Gomes
Sep 23, 2018·Biochemical Society Transactions·Tracy L NeroCraig J Morton
Mar 7, 2019·Current Topics in Medicinal Chemistry·Krishnan Balasubramanian, Satya P Gupta
Nov 3, 2020·Frontiers in Chemistry·Brianda L Santini, Martin Zacharias
Dec 22, 2020·Frontiers in Molecular Biosciences·Irène PitardThérèse E Malliavin
Jun 15, 2021·Journal of Chemical Information and Modeling·Michel F SannerEwa Lis
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana CandalijaJosé Aguilera
Sep 19, 2017·Journal of Chemical Information and Modeling·Nicolas BoscOlivier Sperandio
Apr 23, 2020·ACS Chemical Biology·Nicolas BoscPhilippe Roche
Oct 30, 2015·Future Medicinal Chemistry·Malgorzata Skwarczynska, Christian Ottmann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.