Supplementary Materials

Supplementary Material for:

Indolcarboxamide Is a Preclinical Candidate for Treating Multidrug-Resistant Tuberculosis

Srinivasa P. S. Rao,* Suresh B. Lakshminarayana, Ravinder R. Kondreddi, Maxime Herve, Luis R. Camacho, Pablo Bifani, Sarath K. Kalapala, Jan Jiricek, Ng L. Ma, Bee H. Tan, Seow H. Ng, Mahesh Nanjundappa, Sindhu Ravindran, Peck G. Seah, Pamela Thayalan, Siao H. Lim, Boon H. Lee, Anne Goh, Whitney S. Barnes, Zhong Chen, Kerstin Gagaring, Arnab K. Chatterjee, Kevin Pethe, Kelli Kuhen, John Walker, Gu Feng, Sreehari Babu, Lijun Zhang, Francesca Blasco, David Beer, Margaret Weaver, Veronique Dartois, Richard Glynne, Thomas Dick, Paul W. Smith, Thierry T. Diagana, Ujjini H. Manjunatha*

*Corresponding author. E-mail: manjunatha.ujjini@novartis.com (U.H.M.); srinivasa.rao@novartis.com (S.P.S.R.)

Published 4 December 2013, Sci. Transl. Med. 5, 214ra168 (2013)
DOI: 10.1126/scitranslmed.3007355

This PDF file includes:

  • Methods
  • Fig. S1. Phenotypic HTS cascade to identify the indolcarboxamide series.
  • Fig. S2. Anti-TB activity of NITD-349.
  • Fig. S3. Effect of indolcarboxamides on mycolic acid profiles in Mtb H37Rv and indolcarboxamide-resistant mutants.
  • Fig. S4. Multiple sequence alignment of MmpL3 protein from Mtb, M. bovis BCG, and M. leprae.
  • Fig. S5. A proposed mechanism of action for indolcarboxamides.
  • Fig. S6. Summary of all reported chemical entities showing mutations in MmpL3.
  • Table S1. Activity of indolcarboxamides against various mycobacterial species and broad-spectrum Gram-positive and Gram-negative bacteria.
  • Table S2. Summary of formulations used for NITD-304 and NITD-349 during in vivo mouse efficacy, PK, and toxicology studies.
  • Table S3. Summary of lung Mtb CFU reduction in efficacy studies of acute and established infection in mice.
  • Table S4. Effect of NITD-304 and NITD-349 on ligand binding to a panel of recombinant receptors.
  • References (3850)

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