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Literature summary for 1.3.1.118 extracted from

  • Xia, Y.; Zhou, Y.; Carter, D.; McNeil, M.; Choi, W.; Halladay, J.; Berry, P.; Mao, W.; Hernandez, V.; O'Malley, T.; Korkegian, A.; Sunde, B.; Flint, L.; Woolhiser, L.; Scherman, M.; Gruppo, V.; Hastings, C.; Robertson, G.; Ioerger, T.; Sacchettini, J.
    Discovery of a cofactor-independent inhibitor of Mycobacterium tuberculosis InhA (2018), Life Sci. Alliance, 1, e201800025 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression in Escherichia coli BL-21 Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
D148G diazaborine-resistant mutant Mycobacterium tuberculosis
E219A diazaborine-resistant mutant Mycobacterium tuberculosis
E219G diazaborine-resistant mutant Mycobacterium tuberculosis
I16T diazaborine-resistant mutant Mycobacterium tuberculosis
I202T diazaborine-resistant mutant Mycobacterium tuberculosis
P151S diazaborine-resistant mutant Mycobacterium tuberculosis
R195L diazaborine-resistant mutant Mycobacterium tuberculosis
R195Q diazaborine-resistant mutant Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
2-(ethanesulfonyl)-6-[2-[(E)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
-
Mycobacterium tuberculosis
2-(ethanesulfonyl)-7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol diazaborine, in vitro bactericidal activity against replicating bacteria active against several drug-resistant clinical isolates. AN12855 binds to and inhibits the substrate-binding site of InhA in a cofactor-independent manner. It shows good drug exposure after i.v. and oral delivery, with 53% oral bioavailability. Delivered orally, AN12855 exhibits dose-dependent efficacy in both an acute and chronic murine model of tuberculosis infection. AN12855 is a promising candidate for the development of new antitubercular agents Mycobacterium tuberculosis
4-[[1-hydroxy-2-(methanesulfonyl)-1,2-dihydro-2,3,1-benzodiazaborinin-7-yl]oxy]benzonitrile
-
Mycobacterium tuberculosis
5-[2-[(E)-(hydroxyimino)methyl]phenoxy]-2,1-benzoxaborol-1(3H)-ol
-
Mycobacterium tuberculosis
6-[4-(trifluoromethyl)phenoxy]-2,1-benzoxaborol-1(3H)-ol
-
Mycobacterium tuberculosis
7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2-(methanesulfonyl)-2,3,1-benzodiazaborinin-1(2H)-ol
-
Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WGR1
-
-
Mycobacterium tuberculosis ATCC 25618 P9WGR1
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
InhA
-
Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00003
-
pH 6.8, 23°C Mycobacterium tuberculosis 2-(ethanesulfonyl)-7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
0.0004
-
pH 6.8, 23°C Mycobacterium tuberculosis 7-[2-[(Z)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2-(methanesulfonyl)-2,3,1-benzodiazaborinin-1(2H)-ol
0.0023
-
pH 6.8, 23°C Mycobacterium tuberculosis 2-(ethanesulfonyl)-6-[2-[(E)-(hydroxyimino)methyl]-4-(trifluoromethyl)phenoxy]-2,3,1-benzodiazaborinin-1(2H)-ol
0.012
-
pH 6.8, 23°C Mycobacterium tuberculosis 5-[2-[(E)-(hydroxyimino)methyl]phenoxy]-2,1-benzoxaborol-1(3H)-ol
0.044
-
pH 6.8, 23°C Mycobacterium tuberculosis 6-[4-(trifluoromethyl)phenoxy]-2,1-benzoxaborol-1(3H)-ol
0.079
-
pH 6.8, 23°C Mycobacterium tuberculosis 4-[[1-hydroxy-2-(methanesulfonyl)-1,2-dihydro-2,3,1-benzodiazaborinin-7-yl]oxy]benzonitrile