| Structural highlights
Function
ETHR_MYCTU Involved in the repression of the monooxygenase EthA which is responsible of the formation of the active metabolite of ethionamide (ETH).[1] [2]
Publication Abstract from PubMed
Small molecule inhibitors of the mycobacterial transcriptional repressor EthR have previously been shown to act as boosters of the second-line antituberculosis drug ethionamide. Fragment-based drug discovery approaches have been used in the past to make highly potent EthR inhibitors with ethionamide boosting activity both in vitro and ex vivo. Herein, we report the development of fragment-sized EthR ligands with nanomolar minimum effective concentration (MEC) values for the boosting of ethionamide activity in M. tuberculosis whole cell assays.
Fragment-sized EthR inhibitors exhibit exceptionally strong ethionamide boosting effect in whole cell Mycobacterium tuberculosis assays.,Nikiforov PO, Blaszczyk M, Surade S, Boshoff HI, Sajid A, Delorme V, Deboosere N, Brodin P, Baulard AR, Barry Rd CE, Blundell TL, Abell C ACS Chem Biol. 2017 Mar 17. doi: 10.1021/acschembio.7b00091. PMID:28314097[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Baulard AR, Betts JC, Engohang-Ndong J, Quan S, McAdam RA, Brennan PJ, Locht C, Besra GS. Activation of the pro-drug ethionamide is regulated in mycobacteria. J Biol Chem. 2000 Sep 8;275(36):28326-31. PMID:10869356 doi:10.1074/jbc.M003744200
- ↑ DeBarber AE, Mdluli K, Bosman M, Bekker LG, Barry CE 3rd. Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9677-82. PMID:10944230
- ↑ Nikiforov PO, Blaszczyk M, Surade S, Boshoff HI, Sajid A, Delorme V, Deboosere N, Brodin P, Baulard AR, Barry Rd CE, Blundell TL, Abell C. Fragment-sized EthR inhibitors exhibit exceptionally strong ethionamide boosting effect in whole cell Mycobacterium tuberculosis assays. ACS Chem Biol. 2017 Mar 17. doi: 10.1021/acschembio.7b00091. PMID:28314097 doi:http://dx.doi.org/10.1021/acschembio.7b00091
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