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Please use this identifier to cite or link to this item: https://doi.org/10.1126/scitranslmed.3007355
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dc.titleIndolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis
dc.contributor.authorRao, S.P.S.
dc.contributor.authorLakshminarayana, S.B.
dc.contributor.authorKondreddi, R.R.
dc.contributor.authorHerve, M.
dc.contributor.authorCamacho, L.R.
dc.contributor.authorBifani, P.
dc.contributor.authorKalapala, S.K.
dc.contributor.authorJiricek, J.
dc.contributor.authorMa, N.L.
dc.contributor.authorTan, B.H.
dc.contributor.authorNg, S.H.
dc.contributor.authorNanjundappa, M.
dc.contributor.authorRavindran, S.
dc.contributor.authorSeah, P.G.
dc.contributor.authorThayalan, P.
dc.contributor.authorLim, S.H.
dc.contributor.authorLee, B.H.
dc.contributor.authorGoh, A.
dc.contributor.authorBarnes, W.S.
dc.contributor.authorChen, Z.
dc.contributor.authorGagaring, K.
dc.contributor.authorChatterjee, A.K.
dc.contributor.authorPethe, K.
dc.contributor.authorKuhen, K.
dc.contributor.authorWalker, J.
dc.contributor.authorFeng, G.
dc.contributor.authorBabu, S.
dc.contributor.authorZhang, L.
dc.contributor.authorBlasco, F.
dc.contributor.authorBeer, D.
dc.contributor.authorWeaver, M.
dc.contributor.authorDartois, V.
dc.contributor.authorGlynne, R.
dc.contributor.authorDick, T.
dc.contributor.authorSmith, P.W.
dc.contributor.authorDiagana, T.T.
dc.contributor.authorManjunatha, U.H.
dc.date.accessioned2016-07-08T09:27:56Z
dc.date.available2016-07-08T09:27:56Z
dc.date.issued2013-12-04
dc.identifier.citationRao, S.P.S., Lakshminarayana, S.B., Kondreddi, R.R., Herve, M., Camacho, L.R., Bifani, P., Kalapala, S.K., Jiricek, J., Ma, N.L., Tan, B.H., Ng, S.H., Nanjundappa, M., Ravindran, S., Seah, P.G., Thayalan, P., Lim, S.H., Lee, B.H., Goh, A., Barnes, W.S., Chen, Z., Gagaring, K., Chatterjee, A.K., Pethe, K., Kuhen, K., Walker, J., Feng, G., Babu, S., Zhang, L., Blasco, F., Beer, D., Weaver, M., Dartois, V., Glynne, R., Dick, T., Smith, P.W., Diagana, T.T., Manjunatha, U.H. (2013-12-04). Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis. Science Translational Medicine 5 (214) : -. ScholarBank@NUS Repository. https://doi.org/10.1126/scitranslmed.3007355
dc.identifier.issn19466234
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/125502
dc.description.abstractNew chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drugsensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1126/scitranslmed.3007355
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentMICROBIOLOGY
dc.description.doi10.1126/scitranslmed.3007355
dc.description.sourcetitleScience Translational Medicine
dc.description.volume5
dc.description.issue214
dc.description.page-
dc.identifier.isiut000328057800005
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