2. Academic Validation
  3. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

  • Nat Med. 2013 Sep;19(9):1157-60. doi: 10.1038/nm.3262.
Kevin Pethe 1,  Pablo Bifani,  Jichan Jang,  Sunhee Kang,  Seijin Park,  Sujin Ahn,  Jan Jiricek,  Juyoung Jung,  Hee Kyoung Jeon,  Jonathan Cechetto,  Thierry Christophe,  Honggun Lee,  Marie Kempf,  Mary Jackson,  Anne J Lenaerts,  Ha Pham,  Victoria Jones,  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,  Adeline Chua,  Bee Huat Tan,  Mahesh B Nanjundappa,  Srinivasa P S Rao,  Whitney S Barnes,  René Wintjens,  John R Walker,  Sylvie Alonso,  Saeyeon Lee,  Jungjun Kim,  Soohyun Oh,  Taegwon Oh,  Ulf Nehrbass,  Sung-Jun Han,  Zaesung No,  Jinhwa Lee,  Priscille Brodin,  Sang-Nae Cho,  Kiyean Nam,  Jaeseung Kim
Affiliations

Affiliation

  • 1 1] Institut Pasteur Korea, Sampyeong-dong, Seongnam-si, Gyeonggi-do, Korea. [2].
PMID: 23913123 DOI: 10.1038/nm.3262
Abstract

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis.

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