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Literature summary extracted from

  • Frederickson, M.; Selvam, I.R.; Evangelopoulos, D.; McLean, K.J.; Katariya, M.M.; Tunnicliffe, R.B.; Campbell, B.; Kavanagh, M.E.; Charoensutthivarakul, S.; Blankley, R.T.; Levy, C.W.; de Carvalho, L.P.S.; Leys, D.; Munro, A.W.; Coyne, A.G.; Abell, C.
    A new strategy for hit generation Novel in cellulo active inhibitors of CYP121A1 from Mycobacterium tuberculosis via a combined X-ray crystallographic and phenotypic screening approach (XP screen) (2022), Eur. J. Med. Chem., 230, 114105.
    View publication on PubMed

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.19.70 3-[2-(pyrimidin-4-yl)ethyl]-1H-indole 120% activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(2-(2-(1H-indol-3-yl)ethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)morpholine hydrochloride 151% activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(1-methyl-1H-indol-3-yl)ethyl)pyrimidin-2-yl)morpholine 202% activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(5-fluoro-1H-indol-3-yl)ethyl)pyrimidin-2-yl)morpholine 120% activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-chloro-3-[2-(pyridin-4-yl)ethyl]-1H-indole 104% activity at 0.1 mM Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.14.19.70 sitting drop vapor diffusion method, using 3.5 M (NH4)2SO4 as the precipitant Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.14.19.70 3-(2-(2-(1H-indol-3-yl)ethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane hydrochloride 85% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 3-(2-(2-morpholinopyrimidin-4-yl)ethyl)-1H-indol-5-ol 7% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 3-(2-(pyridin-4-yl)ethyl)-5-(trifluoromethoxy)-1H-indole 42% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 3-[2-(pyridin-4-yl)ethyl]-1H-indole 11% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 3-[2-[2-(1,4-oxazepan-4-yl)pyrimidin-4-yl]ethyl]-1H-indole 32% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(2-(2-(1H-indol-3-yl)ethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)morpholine hydrochloride 19% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(1H-indol-3-yl)ethyl)pyrimidin-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine 4% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(1H-indol-3-yl)ethyl)pyrimidin-2-yl)-6-bromo-3,4-dihydro-2H-benzo[b][1,4]oxazine 12% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(1H-indol-3-yl)ethyl)pyrimidin-2-yl)morpholine 14% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(5-(trifluoromethoxy)-1H-indol-3-yl)ethyl)pyrimidin-2-yl)morpholine 9% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 4-(4-(2-(5-bromo-1H-indol-3-yl)ethyl)pyrimidin-2-yl)morpholine 47% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-bromo-3-(2-(2-(3-methoxyazetidin-1-yl)pyrimidin-4-yl)ethyl)-1H-indole 50% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-bromo-3-[2-(pyridin-4-yl)ethyl]-1H-indole 67% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-fluoro-3-[2-(pyridin-4-yl)ethyl]-1H-indole 62% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-iodo-3-(2-(pyridin-4-yl)ethyl)-1H-indole 80% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 5-methoxy-3-[2-(pyridin-4-yl)ethyl]-1H-indole 5% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 clotrimazole 2% residual activity at 0.1 mM Mycobacterium tuberculosis
1.14.19.70 econazole
-
 Mycobacterium tuberculosis
1.14.19.70 miconazole
-
 Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.19.70 cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 Mycobacterium tuberculosis
-
 mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
 ?
1.14.19.70 cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2 Mycobacterium tuberculosis H37Rv
-
 mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.19.70 Mycobacterium tuberculosis P9WPP7
-
-
1.14.19.70 Mycobacterium tuberculosis H37Rv P9WPP7
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.14.19.70 HisTrap column chromatography and Superdex 75 gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.19.70 cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
-
 Mycobacterium tuberculosis mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
 ?
1.14.19.70 cyclo(L-tyrosyl-L-tyrosyl) + 2 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + O2
-
 Mycobacterium tuberculosis H37Rv mycocyclosin + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.19.70 CYP121A1
-
 Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.14.19.70 0.1
-
 at pH 7.6 and 28°C Mycobacterium tuberculosis 5-bromo-3-(2-(2-(3-methoxyazetidin-1-yl)pyrimidin-4-yl)ethyl)-1H-indole