Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Interfacial inhibitors: targeting macromolecular complexes

Nature Reviews Drug Discovery volume 11, pages 25–36 (2012)Cite this article

Subjects

An Erratum to this article was published on 03 February 2012

This article has been updated

Key Points

  • Interfacial inhibitors belong to a broad class of natural products and synthetic drugs that are commonly used to treat cancers as well as bacterial and HIV infections.

  • They bind selectively to interfaces as macromolecular machines assemble and are set in motion. The bound drugs transiently arrest the targeted molecular machines and desynchronize their concerted functions.

  • To provide an operational (empirical) definition of interfacial inhibition, we present five archetypical examples of interfacial inhibitors: the camptothecins, etoposide, the quinolone antibiotics, the vinca alkaloids and the novel anti-HIV inhibitor raltegravir.

  • We discuss the common and diverging elements between interfacial and allosteric inhibitors, and demonstrate that interfacial inhibitors can also be classified as orthosteric and allosteric inhibitors.

  • Finally, we give a perspective and provide specific examples for the rationale and methods to discover novel interfacial inhibitors.

Abstract

Interfacial inhibitors belong to a broad class of natural products and synthetic drugs that are commonly used to treat cancers as well as bacterial and HIV infections. They bind selectively to interfaces as macromolecular machines assemble and are set in motion. The bound drugs transiently arrest the targeted molecular machines, which can initiate allosteric effects, or desynchronize macromolecular machines that normally function in concert. Here, we review five archetypical examples of interfacial inhibitors: the camptothecins, etoposide, the quinolone antibiotics, the vinca alkaloids and the novel anti-HIV inhibitor raltegravir. We discuss the common and diverging elements between interfacial and allosteric inhibitors and give a perspective for the rationale and methods used to discover novel interfacial inhibitors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Structure of a topoisomerase I cleavage complex trapped by camptothecin.
Figure 2: Structure of a topoisomerase II β cleavage complex trapped by etoposide.
Figure 3: Structure of a topoisomerase IV cleavage complex trapped by the fluoroquinolone antibiotic levofloxacin.
Figure 4: Structure of vinblastine bound in a ternary complex with tubulin heterodimers.
Figure 5: Structure of the retroviral prototype foamy virus intasome in ternary complex with the strand transfer integrase inhibitor raltegravir.

Similar content being viewed by others

Change history

  • 03 February 2012

    In Table 1, the information listed in the 'Substrates' column for 'Etoposide and teniposide' and 'Mitoxantrone' is incorrect; 'TOP1–DNA complex' should be 'TOP2–DNA complex' in both instances. This has been corrected in the online version of the article.

References

  1. Conti, C. et al. Replication fork velocities at adjacent replication origins are coordinately modified during DNA replication in human cells. Mol. Biol. Cell 18, 3059–3067 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sugino, A., Peebles, C. L., Kreuzer, K. N. & Cozzarelli, N. R. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc. Natl Acad. Sci. USA 74, 4767–4771 (1977).

    Article  CAS  Google Scholar 

  3. Gellert, M., Mizuuchi, K., O'Dea, M. H., Itoh, T. & Tomizawa, J. I. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc. Natl Acad. Sci. USA 74, 4772–4776 (1977).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Pommier, Y., Leo, E., Zhang, H. & Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17, 421–433 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Staker, B. L. et al. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc. Natl Acad. Sci. USA 99, 15387–15392 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Staker, B. L. et al. Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex. J. Med. Chem. 48, 2336–2345 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Marchand, C. et al. A novel norindenoisoquinoline structure reveals a common interfacial inhibitor paradigm for ternary trapping of topoisomerase I-DNA covalent complexes. Mol. Cancer Ther. 5, 287–295 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pommier, Y. & Cherfils, J. Interfacial protein inhibition: a nature's paradigm for drug discovery. Trends Pharmacol. Sci. 28, 136–145 (2005).

    Google Scholar 

  9. Pommier, Y. & Marchand, C. Interfacial inhibitors of protein-nucleic acid interactions. Curr. Med. Chem. Anti-Canc. Agents 5, 421–429 (2005).

    Article  CAS  Google Scholar 

  10. Laponogov, I. et al. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nature Struct. Mol. Biol. 16, 667–669 (2009).

    Article  CAS  Google Scholar 

  11. Laponogov, I. et al. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS ONE 5, 8 (2010).

    Article  Google Scholar 

  12. Bax, B. D. et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 466, 935–940 (2010).

    Article  PubMed  Google Scholar 

  13. Hare, S. et al. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc. Natl Acad. Sci. USA 107, 20057–20062 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Krishnan, L. et al. Structure-based modeling of the functional HIV-1 intasome and its inhibition. Proc. Natl Acad. Sci. USA 107, 15910–15915 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hare, S., Gupta, S. S., Valkov, E., Engelman, A. & Cherepanov, P. Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464, 232–236 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wu, C. C. et al. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 333, 459–462 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Forterre, P. in DNA Topoisomerases and Cancer (ed. Pommier, Y.) 1–52 (Springer, New York, 2012).

    Book  Google Scholar 

  18. Chrencik, J. E. et al. Mechanisms of camptothecin resistance by human topoisomerase I mutations. J. Mol. Biol. 339, 773–784 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Koster, D. A., Palle, K., Bot, E. S. M., Bjornsti, M. A. & Dekker, N. H. Antitumour drugs impede DNA uncoiling by topoisomerase I. Nature 448, 213–217 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Pommier, Y., Pourquier, P., Urasaki, Y., Wu, J. & Laco, G. Topoisomerase I inhibitors: selectivity and cellular resistance. Drug Resist. Updat. 2, 307–318 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. Jaxel, C., Kohn, K. W., Wani, M. C., Wall, M. E. & Pommier, Y. Structure–activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res. 49, 1465–1469 (1989).

    CAS  PubMed  Google Scholar 

  22. Eng, W. K., Faucette, L., Johnson, R. K. & Sternglanz, R. Evidence that DNA topoisomerase I is necessary for the cytotoxic effects of camptothecin. Mol. Pharmacol. 34, 755–760 (1988).

    CAS  PubMed  Google Scholar 

  23. Nitiss, J. & Wang, J. C. DNA topoisomerase-targeting antitumor drugs can be studied in yeast. Proc. Natl Acad. Sci. USA 85, 7501–7505 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Sirikantaramas, S., Yamazaki, M. & Saito, K. Mutations in topoisomerase I as a self-resistance mechanism coevolved with the production of the anticancer alkaloid camptothecin in plants. Proc. Natl Acad. Sci. USA 105, 6782–6786 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fujimori, A., Harker, W. G., Kohlhagen, G., Hoki, Y. & Pommier, Y. Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell resistant to camptothecin. Cancer Res. 55, 1339–1346 (1995).

    CAS  PubMed  Google Scholar 

  26. Pommier, Y. Topoisomerase I inhibitors: camptothecins and beyond. Nature Rev. Cancer 6, 789–802 (2006).

    Article  CAS  Google Scholar 

  27. Pommier, Y. et al. Repair of topoisomerase I-mediated DNA damage. Prog. Nucleic Acid Res. Mol. Biol. 81, 179–229 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Capranico, G., Kohn, K. W. & Pommier, Y. Local sequence requirements for DNA cleavage by mammalian topoisomerase II in the presence of doxorubicin. Nucleic Acids Res. 18, 6611–6619 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pommier, Y., Capranico, G., Orr, A. & Kohn, K. W. Local base sequence preferences for DNA cleavage by mammalian topoisomerase II in the presence of amsacrine or teniposide. Nucleic Acids Res. 19, 5973–5980 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Chen, G. L. et al. Nonintercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J. Biol. Chem. 259, 13560–13566 (1984).

    Article  CAS  PubMed  Google Scholar 

  31. Tewey, K. M., Chen, G. L., Nelson, E. M. & Liu, L. F. Intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian DNA topoisomerase II. J. Biol. Chem. 259, 9182–9187 (1984).

    Article  CAS  PubMed  Google Scholar 

  32. Pommier, Y., Capranico, G., Orr, A. & Kohn, K. W. Distribution of topoisomerase II cleavage sites in SV40 DNA and the effects of drugs. J. Mol. Biol. 222, 909–924 (1991).

    Article  CAS  PubMed  Google Scholar 

  33. Capranico, G., Zunino, F., Kohn, K. W. & Pommier, Y. Sequence-selective topoisomerase II inhibition by anthracycline derivatives in SV40 DNA: relationship with DNA binding affinity and cytotoxicity. Biochemistry 29, 562–569 (1990).

    Article  CAS  PubMed  Google Scholar 

  34. Capranico, G., De Isabella, P., Tinelli, S., Bigioni, S. & Zunino, F. Similar sequence specificity of mitoxantrone and VM-26 stimulation of in vitro DNA cleavage by mammalian DNA topoisomerase II. Biochemistry 32, 3032–3048 (1993).

    Google Scholar 

  35. Heddle, J. G., Barnard, F. M., Wentzell, L. M. & Maxwell, A. The interaction of drugs with DNA gyrase: a model for the molecular basis of quinolone action. Nucleosides Nucleotides Nucleic Acids 19, 1249–1264 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. De Jonge, N. et al. Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain. Mol. Cell 35, 154–163 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Williams, J. J. & Hergenrother, P. J. Exposing plasmids as the Achilles' heel of drug-resistant bacteria. Curr. Opin. Chem. Biol. 12, 389–399 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Dao-Thi, M. H. et al. Molecular basis of gyrase poisoning by the addiction toxin CcdB. J. Mol. Biol. 348, 1091–1102 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Ishida, R. et al. Inhibition of DNA topoisomerase II by ICRF-193 induces polyploidization by uncoupling chromosome dynamics from other cell cycle events. J. Cell Biol. 126, 1341–1351 (1994).

    Article  CAS  PubMed  Google Scholar 

  40. Andoh, T. & Ishida, R. Catalytic inhibitors of DNA topoisomerase II. Biochim. Biophys. Acta 1400, 155–171 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. Classen, S., Olland, S. & Berger, J. M. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Proc. Natl Acad. Sci. USA 100, 10629–10634 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Dumontet, C. & Jordan, M. A. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nature Rev. Drug Discov. 9, 790–803 (2010).

    Article  CAS  Google Scholar 

  43. Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nature Rev. Cancer 4, 253–265 (2004).

    Article  CAS  Google Scholar 

  44. Gigant, B. et al. Structural basis for the regulation of tubulin by vinblastine. Nature 435, 519–522 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Hare, S. et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol. Pharmacol. 80, 565–572 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Marchand, C., Maddali, K., Metifiot, M. & Pommier, Y. HIV-1 IN inhibitors: 2010 update and perspectives. Curr. Top. Med. Chem. 9, 1016–1037 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Metifiot, M., Marchand, C., Maddali, K. & Pommier, Y. Resistance to integrase inhibitors. Viruses 2, 1347–1366 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Metifiot, M. et al. Elvitegravir overcomes resistance to raltegravir induced by integrase mutation Y143. AIDS 25, 1175–1178 (2011).

    Article  CAS  PubMed  Google Scholar 

  49. Pommier, Y., Johnson, A. & Marchand, C. Integrase inhibitors to treat HIV/AIDS. Nature Rev. Drug Discov. 4, 236–248 (2005).

    Article  CAS  Google Scholar 

  50. Li, X., Krishnan, L., Cherepanov, P. & Engelman, A. Structural biology of retroviral DNA integration. Virology 411, 194–205 (2011).

    Article  CAS  PubMed  Google Scholar 

  51. Zhao, X. Z. et al. Development of tricyclic hydroxy-1H-pyrrolopyridine-trione containing HIV-1 integrase inhibitors. Bioorg. Med. Chem. Lett. 21, 2986–2990 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wells, J. A. & McClendon, C. L. Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature 450, 1001–1009 (2007).

    Article  CAS  PubMed  Google Scholar 

  53. Changeux, J. P. & Taly, A. Nicotinic receptors, allosteric proteins and medicine. Trends Mol. Med. 14, 93–102 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Burgin, A. B. et al. Design of phosphodiesterase 4D (PDE4D) allosteric modulators for enhancing cognition with improved safety. Nature Biotech. 28, 63–70 (2010).

    Article  CAS  Google Scholar 

  55. Changeux, J.-P. 50th anniversary of the word “allosteric”. Protein Science 20, 1119–1124 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Monod, J., Changeux, J. P. & Jacob, F. Allosteric proteins and cellular control systems. J. Mol. Biol. 6, 306–329 (1963).

    Article  CAS  PubMed  Google Scholar 

  57. Pommier, Y. et al. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the carribean tunicate Ecteinascidia Turbinata. Biochemistry 35, 13303–13309 (1996).

    Article  CAS  PubMed  Google Scholar 

  58. Koshland, D. E. Jr, Nemethy, G. & Filmer, D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 5, 365–385 (1966).

    Article  CAS  PubMed  Google Scholar 

  59. Maertens, G. N., Hare, S. & Cherepanov, P. The mechanism of retroviral integration from X-ray structures of its key intermediates. Nature 468, 326–329 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Brueckner, F. & Cramer, P. Structural basis of transcription inhibition by α-amanitin and implications for RNA polymerase II translocation. Nature Struct. Mol. Biol. 15, 811–818 (2008).

    Article  CAS  Google Scholar 

  61. Bushnell, D. A., Cramer, P. & Kornberg, R. D. Structural basis of transcription: α-amanitin–RNA polymerase II cocrystal at 2.8 Å resolution. Proc. Natl Acad. Sci. USA 99, 1218–1222 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hibbs, R. E. et al. Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal α7 nicotinic acetylcholine receptor. EMBO J. 28, 3040–3051 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nury, H. et al. X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel. Nature 469, 428–431 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Sigel, E. & Luscher, B. P. A closer look at the high affinity benzodiazepine binding site on GABAA receptors. Curr. Top. Med. Chem. 11, 241–246 (2011).

    Article  CAS  PubMed  Google Scholar 

  65. Renault, L., Guibert, B. & Cherfils, J. Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor. Nature 426, 525–530 (2003).

    Article  CAS  PubMed  Google Scholar 

  66. Mossessova, E., Corpina, R. A. & Goldberg, J. Crystal structure of ARF1• Sec7 complexed with Brefeldin A and its implications for the guanine nucleotide exchange mechanism. Mol. Cell 12, 1403–1411 (2003).

    Article  CAS  PubMed  Google Scholar 

  67. Ravelli, R. B. G. et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature 428, 198–202 (2004).

    Article  CAS  PubMed  Google Scholar 

  68. Jin, L. & Harrison, S. C. Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin. Proc. Natl Acad. Sci. USA 99, 13522–13526 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huai, Q. et al. Crystal structure of calcineurin–cyclophilin–cyclosporin shows common but distinct recognition of immunophilin–drug complexes. Proc. Natl Acad. Sci. USA 99, 12037–12042 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Roca, J., Ishida, R., Berger, J. M., Andoh, T. & Wang, J. C. Antitumor bisdioxopiperazines inhibit yeast DNA topoisomerase II by trapping the enzyme in the form of a closed protein clamp. Proc. Natl Acad. Sci. USA 91, 1781–1785 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Takebayashi, Y. et al. Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nature Med. 7, 961–966 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Nettles, J. H. et al. The binding mode of epothilone A on α,β-tubulin by electron crystallography. Science 305, 866–869 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Kissinger, C. R. et al. Crystal structures of human calcineurin and the human FKBP12–FK506–calcineurin complex. Nature 378, 641–644 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Griffith, J. P. et al. X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex. Cell 82, 507–522 (1995).

    Article  CAS  PubMed  Google Scholar 

  75. Tesmer, J. J., Sunahara, R. K., Gilman, A. G. & Sprang, S. R. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsα•GTPγS. Science 278, 1907–1916 (1997).

    Article  CAS  PubMed  Google Scholar 

  76. Wurtele, M., Jelich-Ottmann, C., Wittinghofer, A. & Oecking, C. Structural view of a fungal toxin acting on a 14-3-3 regulatory complex. EMBO J. 22, 987–994 (2003).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Agrawal, R. K. & Frank, J. Structural studies of the translational apparatus. Curr. Opin. Struct. Biol. 9, 215–221 (1999).

    Article  CAS  PubMed  Google Scholar 

  78. Laurberg, M. et al. Structure of a mutant EF-G reveals domain III and possibly the fusidic acid binding site. J. Mol. Biol. 303, 593–603 (2000).

    Article  CAS  PubMed  Google Scholar 

  79. Ioanoviciu, A. et al. Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA–enzyme–inhibitor complex as determined by X-ray crystallographic analysis. J. Med. Chem. 48, 4803–4814 (2005).

    Article  CAS  PubMed  Google Scholar 

  80. Choi, J., Chen, J., Schreiber, S. L. & Clardy, J. Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273, 239–242 (1996).

    Article  CAS  PubMed  Google Scholar 

  81. Moellering, R. E. et al. Direct inhibition of the NOTCH transcription factor complex. Nature 462, 182–188 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Edwards, M. J. et al. A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase. Science 326, 1415–1418 (2009).

    Article  CAS  PubMed  Google Scholar 

  83. Snyder, J. P., Nettles, J. H., Cornett, B., Downing, K. H. & Nogales, E. The binding conformation of taxol in β-tubulin: a model based on electron crystallographic density. Proc. Natl Acad. Sci. USA 98, 5312–5316 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Bowen, W. S., Van Dyke, N., Murgola, E. J., Lodmell, J. S. & Hill, W. E. Interaction of thiostrepton and elongation factor-G with the ribosomal protein L11-binding domain. J. Biol. Chem. 280, 2934–2943 (2004).

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Our studies are supported by the Center for Cancer Research, the Intramural Program of the National Cancer Institute, US National Institutes of Health.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, 20892, Maryland, USA

    Yves Pommier & Christophe Marchand

Authors
  1. Yves Pommier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christophe Marchand
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yves Pommier.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Yves Pommier's homepage

Christophe Marchand's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pommier, Y., Marchand, C. Interfacial inhibitors: targeting macromolecular complexes. Nat Rev Drug Discov 11, 25–36 (2012). https://doi.org/10.1038/nrd3404

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrd3404

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer