Please use this identifier to cite or link to this item:
|Title:||Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis||Authors:||Rao, S.P.S.
|Issue Date:||4-Dec-2013||Citation:||Rao, 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||Abstract:||New 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.||Source Title:||Science Translational Medicine||URI:||http://scholarbank.nus.edu.sg/handle/10635/125502||ISSN:||19466234||DOI:||10.1126/scitranslmed.3007355|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.