IPPI-DB: an Online Database of Modulators of Protein-protein Interactions

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2015 Oct 4

PMID 26432833

Citations 21

Authors

Celine M Labbe

Melaine A Kuenemann

Barbara Zarzycka

Gert Vriend

Gerry A F Nicolaes

David Lagorce

Maria A Miteva

Bruno O Villoutreix

Olivier Sperandio

Affiliations

Soon will be listed here.

Abstract

In order to boost the identification of low-molecular-weight drugs on protein-protein interactions (PPI), it is essential to properly collect and annotate experimental data about successful examples. This provides the scientific community with the necessary information to derive trends about privileged physicochemical properties and chemotypes that maximize the likelihood of promoting a given chemical probe to the most advanced stages of development. To this end we have developed iPPI-DB (freely accessible at http://www.ippidb.cdithem.fr), a database that contains the structure, some physicochemical characteristics, the pharmacological data and the profile of the PPI targets of several hundreds modulators of protein-protein interactions. iPPI-DB is accessible through a web application and can be queried according to two general approaches: using physicochemical/pharmacological criteria; or by chemical similarity to a user-defined structure input. In both cases the results are displayed as a sortable and exportable datasheet with links to external databases such as Uniprot, PubMed. Furthermore each compound in the table has a link to an individual ID card that contains its physicochemical and pharmacological profile derived from iPPI-DB data. This includes information about its binding data, ligand and lipophilic efficiencies, location in the PPI chemical space, and importantly similarity with known drugs, and links to external databases like PubChem, and ChEMBL.

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References

Lagorce D, Sperandio O, Baell J, Miteva M, Villoutreix B . FAF-Drugs3: a web server for compound property calculation and chemical library design. Nucleic Acids Res. 2015; 43(W1):W200-7. PMC: 4489254. DOI: 10.1093/nar/gkv353. View

Higueruelo A, Schreyer A, Bickerton G, Pitt W, Groom C, Blundell T . Atomic interactions and profile of small molecules disrupting protein-protein interfaces: the TIMBAL database. Chem Biol Drug Des. 2009; 74(5):457-67. DOI: 10.1111/j.1747-0285.2009.00889.x. View

Basse M, Betzi S, Bourgeas R, Bouzidi S, Chetrit B, Hamon V . 2P2Idb: a structural database dedicated to orthosteric modulation of protein-protein interactions. Nucleic Acids Res. 2012; 41(Database issue):D824-7. PMC: 3531195. DOI: 10.1093/nar/gks1002. View

Hughes J, Blagg J, Price D, Bailey S, DeCrescenzo G, Devraj R . Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008; 18(17):4872-5. DOI: 10.1016/j.bmcl.2008.07.071. View

Arkin M, Tang Y, Wells J . Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol. 2014; 21(9):1102-14. PMC: 4179228. DOI: 10.1016/j.chembiol.2014.09.001. View

Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F . ChEMBL web services: streamlining access to drug discovery data and utilities. Nucleic Acids Res. 2015; 43(W1):W612-20. PMC: 4489243. DOI: 10.1093/nar/gkv352. View

Yu M, Wang Y, Zhu J, Bartberger M, Canon J, Chen A . Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2-p53 Interaction. ACS Med Chem Lett. 2014; 5(8):894-9. PMC: 4137378. DOI: 10.1021/ml500142b. View

Jubb H, Higueruelo A, Winter A, Blundell T . Structural biology and drug discovery for protein-protein interactions. Trends Pharmacol Sci. 2012; 33(5):241-8. DOI: 10.1016/j.tips.2012.03.006. View

Kuenemann M, Sperandio O, Labbe C, Lagorce D, Miteva M, Villoutreix B . In silico design of low molecular weight protein-protein interaction inhibitors: Overall concept and recent advances. Prog Biophys Mol Biol. 2015; 119(1):20-32. DOI: 10.1016/j.pbiomolbio.2015.02.006. View

10.

Morelli X, Bourgeas R, Roche P . Chemical and structural lessons from recent successes in protein-protein interaction inhibition (2P2I). Curr Opin Chem Biol. 2011; 15(4):475-81. DOI: 10.1016/j.cbpa.2011.05.024. View

11.

Labbe C, Rey J, Lagorce D, Vavrusa M, Becot J, Sperandio O . MTiOpenScreen: a web server for structure-based virtual screening. Nucleic Acids Res. 2015; 43(W1):W448-54. PMC: 4489289. DOI: 10.1093/nar/gkv306. View

12.

Sperandio O, Reynes C, Camproux A, Villoutreix B . Rationalizing the chemical space of protein-protein interaction inhibitors. Drug Discov Today. 2009; 15(5-6):220-9. DOI: 10.1016/j.drudis.2009.11.007. View

13.

Veber D, Johnson S, Cheng H, Smith B, Ward K, Kopple K . Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002; 45(12):2615-23. DOI: 10.1021/jm020017n. View

14.

Villoutreix B, Kuenemann M, Poyet J, Bruzzoni-Giovanelli H, Labbe C, Lagorce D . Drug-Like Protein-Protein Interaction Modulators: Challenges and Opportunities for Drug Discovery and Chemical Biology. Mol Inform. 2014; 33(6-7):414-437. PMC: 4160817. DOI: 10.1002/minf.201400040. View

15.

Ritchie T, Macdonald S . The impact of aromatic ring count on compound developability--are too many aromatic rings a liability in drug design?. Drug Discov Today. 2009; 14(21-22):1011-20. DOI: 10.1016/j.drudis.2009.07.014. View

16.

Hopkins A, Keseru G, Leeson P, Rees D, Reynolds C . The role of ligand efficiency metrics in drug discovery. Nat Rev Drug Discov. 2014; 13(2):105-21. DOI: 10.1038/nrd4163. View

17.

Rose P, Prlic A, Bi C, Bluhm W, Christie C, Dutta S . The RCSB Protein Data Bank: views of structural biology for basic and applied research and education. Nucleic Acids Res. 2014; 43(Database issue):D345-56. PMC: 4383988. DOI: 10.1093/nar/gku1214. View

18.

Higueruelo A, Jubb H, Blundell T . TIMBAL v2: update of a database holding small molecules modulating protein-protein interactions. Database (Oxford). 2013; 2013:bat039. PMC: 3681332. DOI: 10.1093/database/bat039. View

19.

. Database resources of the National Center for Biotechnology Information. Nucleic Acids Res. 2014; 43(Database issue):D6-17. PMC: 4383943. DOI: 10.1093/nar/gku1130. View

20.

Labbe C, Laconde G, Kuenemann M, Villoutreix B, Sperandio O . iPPI-DB: a manually curated and interactive database of small non-peptide inhibitors of protein-protein interactions. Drug Discov Today. 2013; 18(19-20):958-68. DOI: 10.1016/j.drudis.2013.05.003. View