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Literature summary for 6.1.1.10 extracted from

  • Torrie, L.S.; Brand, S.; Robinson, D.A.; Ko, E.J.; Stojanovski, L.; Simeons, F.R.C.; Wyllie, S.; Thomas, J.; Ellis, L.; Osuna-Cabello, M.; Epemolu, O.; Nuehs, A.; Riley, J.; MacLean, L.; Manthri, S.; Read, K.D.; Gilbert, I.H.; Fairlamb, A.H.; De Rycker, M.
    Chemical validation of methionyl-tRNA synthetase as a druggable target in Leishmania donovani (2017), ACS Infect. Dis., 3, 718-727 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli BL21(DE3) cells Leishmania donovani

Inhibitors

Inhibitors Comment Organism Structure
2-(3-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]propoxy)quinazolin-4(1H)-one
-
Leishmania donovani
2-[(3-[[(3,5-dichlorophenyl)methyl]amino]propyl)amino]quinazolin-4(1H)-one
-
Leishmania donovani
2-[(3-[[(4,6-dichloro-1H-indol-2-yl)methyl](methyl)amino]propyl)amino]quinazolin-4(1H)-one
-
Leishmania donovani
2-[(3-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]propyl)amino]quinazolin-4(1H)-one DDDD806905, highly potent inhibitor, competitive inhibition with respect to L-methionine Leishmania donovani
2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-6-(trifluoromethyl)-1H-indole-4-peroxol
-
Leishmania donovani
2-[2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-4,6-dichloro-1H-indol-1-yl]ethan-1-ol
-
Leishmania donovani
2-[[5-(3,5-dichlorophenyl)pentyl]amino]quinazolin-4(1H)-one
-
Leishmania donovani
3,5-dichloro-N-[3-[(4-oxo-1,4-dihydroquinazolin-2-yl)amino]propyl]benzene-1-sulfonamide
-
Leishmania donovani
ATP substrate inhibition Leishmania donovani
N-[(3,5-dichlorophenyl)methyl]-3-[(4-oxo-1,4-dihydroquinazolin-2-yl)amino]propanamide
-
Leishmania donovani
N-[3-[(1H-benzimidazol-2-yl)amino]propyl]-3-(trifluoromethoxy)benzamide
-
Leishmania donovani
N-[[(1R)-2-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]cyclopentyl]methyl]-1H-benzimidazol-2-amine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-(6,8-dichloro-3,4-dihydro-2H-1-benzopyran-4-yl)propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(3,5-dichloro-2-ethoxyphenyl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(3,6-dichloro-1H-indol-2-yl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(3-bromo-2-ethoxy-5-methylphenyl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(3-bromo-5-chloro-2-ethoxyphenyl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(4,6-dichloro-3-methyl-1H-indol-2-yl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[(4,7-dichloro-1H-indol-2-yl)methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[[4,6-bis(trifluoromethyl)-1H-indol-2-yl]methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(1H-benzimidazol-2-yl)-N3-[[6-methoxy-4-(trifluoromethyl)-1H-indol-2-yl]methyl]propane-1,3-diamine
-
Leishmania donovani
N1-(6,8-dibromo-1,2,3,4-tetrahydroquinolin-4-yl)-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[(3,5-dibromophenyl)methyl]-N3-(7-methoxy-1H-benzimidazol-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[(3,5-dichloro-4-propylphenyl)methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[(4,5-dibromo-3-methylthiophen-2-yl)methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[(4,6-dimethyl-1H-indol-2-yl)methyl]-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[(5-bromo-2-ethoxy-3-methoxyphenyl)methyl]-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[[4-bromo-5-(1-fluoroethenyl)-3-methylthiophen-2-yl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[[4-bromo-5-(difluoromethyl)-3-methylthiophen-2-yl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
N1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)-2-propylpropane-1,3-diamine
-
Leishmania donovani
N1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
-
Leishmania donovani
[2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-4,6-dichlorophenyl]methanol
-
Leishmania donovani

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.037
-
ATP at pH 8.0 and 25°C Leishmania donovani
0.173
-
L-methionine at pH 8.0 and 25°C Leishmania donovani

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-methionine + tRNAMet Leishmania donovani
-
AMP + diphosphate + L-methionyl-tRNAMet
-
?

Organism

Organism UniProt Comment Textmining
Leishmania donovani
-
-
-

Purification (Commentary)

Purification (Comment) Organism
HiTrap His column chromatography and Superdex 200 gel filtration Leishmania donovani

Source Tissue

Source Tissue Comment Organism Textmining

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-methionine + tRNAMet
-
Leishmania donovani AMP + diphosphate + L-methionyl-tRNAMet
-
?

Synonyms

Synonyms Comment Organism
methionyl-tRNA synthetase
-
Leishmania donovani
MetRS
-
Leishmania donovani

Cofactor

Cofactor Comment Organism Structure
ATP
-
Leishmania donovani

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000018
-
2-[(3-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]propyl)amino]quinazolin-4(1H)-one at pH 8.0 and 25°C Leishmania donovani
0.482
-
ATP at pH 8.0 and 25°C Leishmania donovani

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00009
-
at pH 8.0 and 25°C Leishmania donovani 2-[(3-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]propyl)amino]quinazolin-4(1H)-one
0.00017
-
at pH 8.0 and 25°C Leishmania donovani N1-(6,8-dibromo-1,2,3,4-tetrahydroquinolin-4-yl)-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
0.00038
-
at pH 8.0 and 25°C Leishmania donovani 2-[2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-4,6-dichloro-1H-indol-1-yl]ethan-1-ol
0.0017
-
at pH 8.0 and 25°C Leishmania donovani N-[[(1R)-2-[[(4,6-dichloro-1H-indol-2-yl)methyl]amino]cyclopentyl]methyl]-1H-benzimidazol-2-amine
0.002
-
at pH 8.0 and 25°C Leishmania donovani N1-[[4-bromo-5-(1-fluoroethenyl)-3-methylthiophen-2-yl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
0.0021
-
at pH 8.0 and 25°C Leishmania donovani N1-[(4,5-dibromo-3-methylthiophen-2-yl)methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
0.0028
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(4,6-dichloro-3-methyl-1H-indol-2-yl)methyl]propane-1,3-diamine
0.0039
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-(6,8-dichloro-3,4-dihydro-2H-1-benzopyran-4-yl)propane-1,3-diamine
0.0048
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[[6-methoxy-4-(trifluoromethyl)-1H-indol-2-yl]methyl]propane-1,3-diamine
0.0054
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(3,5-dichloro-2-ethoxyphenyl)methyl]propane-1,3-diamine
0.0056
-
at pH 8.0 and 25°C Leishmania donovani N1-[(4,6-dimethyl-1H-indol-2-yl)methyl]-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
0.0059
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(3-bromo-5-chloro-2-ethoxyphenyl)methyl]propane-1,3-diamine
0.0089
-
at pH 8.0 and 25°C Leishmania donovani N1-[[4-bromo-5-(difluoromethyl)-3-methylthiophen-2-yl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
0.01
-
at pH 8.0 and 25°C Leishmania donovani N1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
0.012
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(3-bromo-2-ethoxy-5-methylphenyl)methyl]propane-1,3-diamine
0.014
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(3,6-dichloro-1H-indol-2-yl)methyl]propane-1,3-diamine
0.037
-
at pH 8.0 and 25°C Leishmania donovani N1-[(5-bromo-2-ethoxy-3-methoxyphenyl)methyl]-N3-(1H-imidazo[4,5-b]pyridin-2-yl)propane-1,3-diamine
0.044
-
at pH 8.0 and 25°C Leishmania donovani N1-[(3,5-dichloro-4-propylphenyl)methyl]-N3-(3H-imidazo[4,5-c]pyridin-2-yl)propane-1,3-diamine
0.046
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[[4,6-bis(trifluoromethyl)-1H-indol-2-yl]methyl]propane-1,3-diamine
0.047
-
at pH 8.0 and 25°C Leishmania donovani [2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-4,6-dichlorophenyl]methanol
0.055
-
at pH 8.0 and 25°C Leishmania donovani N1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]-N3-(1H-imidazo[4,5-c]pyridin-2-yl)-2-propylpropane-1,3-diamine
0.069
-
at pH 8.0 and 25°C Leishmania donovani N1-(1H-benzimidazol-2-yl)-N3-[(4,7-dichloro-1H-indol-2-yl)methyl]propane-1,3-diamine
0.079
-
at pH 8.0 and 25°C Leishmania donovani N1-[(3,5-dibromophenyl)methyl]-N3-(7-methoxy-1H-benzimidazol-2-yl)propane-1,3-diamine
0.1
-
IC50 above 0.1 mM, at pH 8.0 and 25°C Leishmania donovani 2-[([3-[(1H-benzimidazol-2-yl)amino]propyl]amino)methyl]-6-(trifluoromethyl)-1H-indole-4-peroxol
0.1
-
IC50 above 0.1 mM, at pH 8.0 and 25°C Leishmania donovani N-[3-[(1H-benzimidazol-2-yl)amino]propyl]-3-(trifluoromethoxy)benzamide