Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis (original) (raw)

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Acknowledgements

This work was supported by a National Research Foundation of Korea grant funded by the Korean government Ministry of Education, Science and Technology (2012-00011), the Korea Institute of Science and Technology Information, Gyeonggi-do and Institut National de la Santé et de la Recherche Médicale-Avenir. R.W. received support from the Belgian Fund for Scientific Research. We thank T. Diagana and P. Smith for critical reading of the manuscript.

Author information

Author notes

  1. Zaesung No
    Present address: Present address: Gyeonggi Biocenter, Suwon-si, Gyeonggi-do, Korea.,
  2. Kevin Pethe and Pablo Bifani: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut Pasteur Korea, Sampyeong-dong, Seongnam-si, Gyeonggi-do, Korea
    Kevin Pethe, Jichan Jang, Sunhee Kang, Seijin Park, Sujin Ahn, Hee Kyoung Jeon, Jonathan Cechetto, Thierry Christophe, Honggun Lee, Min Jung Seo, Young Mi Kim, Mooyoung Seo, Jeong Jea Seo, Dongsik Park, Yoonae Ko, Inhee Choi, Ryangyeo Kim, Se Yeon Kim, SeungBin Lim, Seung-Ae Yim, Jiyoun Nam, Hwankyu Kang, Haejin Kwon, Chun-Taek Oh, Yoojin Cho, Yunhee Jang, Junghwan Kim, Saeyeon Lee, Ulf Nehrbass, Sung-Jun Han, Zaesung No, Jinhwa Lee, Priscille Brodin & Jaeseung Kim
  2. Novartis Institute for Tropical Diseases, Singapore
    Pablo Bifani, Jan Jiricek, Adeline Chua, Bee Huat Tan, Mahesh B Nanjundappa & Srinivasa P S Rao
  3. Department of Veterinary Histology, College of Veterinary Medicine, Chungnam National University, Daejeon, Korea
    Juyoung Jung
  4. Groupe d'Étude des Interactions Hôte-Pathogène, Université d'Angers et Laboratoire de Bactériologie, Centre Hospitalier Universitaire d'Angers, France
    Marie Kempf
  5. Department of Microbiology, Mycobacteria Research Laboratories, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA
    Mary Jackson, Anne J Lenaerts, Ha Pham & Victoria Jones
  6. Genomics Institute of the Novartis Research Foundation, San Diego, California, USA
    Whitney S Barnes & John R Walker
  7. Structural Biology Unit, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies, Belgium
    René Wintjens
  8. Department of Microbiology and Immunology Programme, Yong Loo Lin School of Medicine, Life Sciences Institute, National University of Singapore, Singapore
    Sylvie Alonso
  9. Qurient, Sampyeong-dong, Seongnam-si, Gyeonggi-do, Korea
    Jungjun Kim, Soohyun Oh & Kiyean Nam
  10. Department of Microbiology and Immunology, College of Medicine, Yonsei University, Seoul, Korea
    Taegwon Oh & Sang-Nae Cho

Authors

  1. Kevin Pethe
  2. Pablo Bifani
  3. Jichan Jang
  4. Sunhee Kang
  5. Seijin Park
  6. Sujin Ahn
  7. Jan Jiricek
  8. Juyoung Jung
  9. Hee Kyoung Jeon
  10. Jonathan Cechetto
  11. Thierry Christophe
  12. Honggun Lee
  13. Marie Kempf
  14. Mary Jackson
  15. Anne J Lenaerts
  16. Ha Pham
  17. Victoria Jones
  18. Min Jung Seo
  19. Young Mi Kim
  20. Mooyoung Seo
  21. Jeong Jea Seo
  22. Dongsik Park
  23. Yoonae Ko
  24. Inhee Choi
  25. Ryangyeo Kim
  26. Se Yeon Kim
  27. SeungBin Lim
  28. Seung-Ae Yim
  29. Jiyoun Nam
  30. Hwankyu Kang
  31. Haejin Kwon
  32. Chun-Taek Oh
  33. Yoojin Cho
  34. Yunhee Jang
  35. Junghwan Kim
  36. Adeline Chua
  37. Bee Huat Tan
  38. Mahesh B Nanjundappa
  39. Srinivasa P S Rao
  40. Whitney S Barnes
  41. René Wintjens
  42. John R Walker
  43. Sylvie Alonso
  44. Saeyeon Lee
  45. Jungjun Kim
  46. Soohyun Oh
  47. Taegwon Oh
  48. Ulf Nehrbass
  49. Sung-Jun Han
  50. Zaesung No
  51. Jinhwa Lee
  52. Priscille Brodin
  53. Sang-Nae Cho
  54. Kiyean Nam
  55. Jaeseung Kim

Contributions

Jaeseung Kim, K.N. and K.P. supervised the project, H.K.J., J.C., P. Brodin, T.C., H.L., K.P., R.K., S.-A.Y., U.N. and J. Jang designed and performed the chemical genetics screen and growth inhibition experiments, S. Kang, M.J.S., S. Lee, Y.M.K., M.S., J.J.S., D.P., Y.K., I.C., Jaeseung Kim, Z.N., J.L. and J. Jiricek designed and synthesized the compounds, J. Jang, K.P. and S.Y.K. designed and performed the ATP quantification experiments, K.P., J. Jang, S. Alonso, C.-T.O., Y.C., Y.J., Junghwan Kim, S.-J.H., M.J., H.P., P. Bifani and V.J. designed and performed the mode of action studies, S.P., S. Ahn, H. Kang, H. Kwon, J.N., S. Lim, K.N. and A.J.L. performed and designed in vivo pharmacokinetic and efficacy experiments, J. Jung and A.J.L. performed and interpreted the histopathology experiments, S. Ahn, K.N., S.O. and Jungjun Kim designed or managed the in vitro toxicology assessment and the in vitro pharmacokinetic profiling, J.R.W. and W.S.B. designed and performed the whole-genome sequencing experiments, T.O. and S.-N.C. tested Q203 against MDR and XDR clinical isolates and other mycobacteria, Y.K., I.C. and R.W. performed bioinformatics analysis, P. Bifani, A.C., B.H.T., M.B.N., S.P.S.R., K.P. and S.-A.Y. designed and performed experiments for target validation, M.K. tested Q203 against a panel of microorganisms, K.P. wrote the manuscript with contributions from other authors.

Corresponding authors

Correspondence toKevin Pethe, Kiyean Nam or Jaeseung Kim.

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Competing interests

K.N., Jungjun Kim, S.O. and S.L. are employees of Qurient, which has been developing Q203 as a therapeutic agent against MDR and XDR tuberculosis. Jaeseung Kim, S.-J.H., J.L., S.L., U.N. and P. Bordin have shares in Qurient.

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Pethe, K., Bifani, P., Jang, J. et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis.Nat Med 19, 1157–1160 (2013). https://doi.org/10.1038/nm.3262

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