Literature summary for 5.6.2.1 extracted from

Bond, A.; Reichert, Z.; Stivers, J.T.
Novel and specific inhibitors of a poxvirus type I topoisomerase (2006), Mol. Pharmacol., 69, 547-557.

Application

Application	Comment	Organism
drug development	potential target for drug treatment against smallpox and molluscum contagiosum virus	Homo sapiens
drug development	potential target for drug treatment against smallpox and molluscum contagiosum virus	Vaccinia virus

Cloned(Commentary)

Cloned (Comment)	Organism
-	Vaccinia virus

Protein Variants

Protein Variants	Comment	Organism
Y274F	vaccinia topoisomerase mutant, lacks active site tyrosine nucleophile but binds to DNA containing specific recognition sequence, like wild type vTopo	Vaccinia virus

Inhibitors

Inhibitors	Comment	Organism
1,2'-binaphthalene-7',8-dicarboxylic acid	does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 0%	Vaccinia virus
1,3-bis(4-amino-2-methylquinolin-6-yl)urea	IC90 (compound concentration at which 90% or higher inhibition is observed) 2 microM, using high-throughput screen, relaxation inhibition 40%	Vaccinia virus
1-(3,4-dihydroxybenzyl)isoquinoline-6,7-diol	IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 80%	Vaccinia virus
1-[3-[(dicyclohexylamino)methyl]-2,4-dihydroxyphenyl]ethanone	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
17-beta-3-oxo-18-norandrost-4-ene-17-carboxylic acid -4-bromo-benzene sulfonic acid ester	partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM	Homo sapiens
17-beta-3-oxo-18-Norandrost-4-ene-17-carboxylic acid-4-bromo-benzene sulfonic acid ester	shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
2-methylidenebutanedioic acid	IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
2-[[2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-chromen-3-yl]oxy]-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-chromene-3,4,5,7-tetrol	IC90 (compound concentration at which 90% or higher inhibition is observed) 0.5 microM, using high-throughput screen, relaxation inhibition 70%; IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
4,4',4'',4'''-ethane-1,1,2,2-tetrayltetrakis(2,6-dichlorophenol)	IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 60%	Vaccinia virus
4,4-bis(3,5-dibromo-4-hydroxyphenyl)pentanoic acid	IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
4-[(2-carboxyphenyl)carbonyl]benzene-1,2-dicarboxylic acid	IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
4-[(6-chloro-2-methoxyacridin-9-yl)amino]-2-[(4-methylpiperazin-1-yl)methyl]phenol	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
4-[[(2-fluorophenyl)carbamoyl]amino]benzenesulfonamide	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 40%	Vaccinia virus
4-[[2-(6-amino-8-oxo-1,2,3,4,5,8-hexahydropyrido[2,3-b]pyrazin-2-yl)ethyl]amino]benzoic acid	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
5,5'-(1,1'-dihydroxy-8,8'-dimethoxy-6,6'-dimethyl-2,2'-binaphthalene-4,4'-diyl)bis(1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline-6,8-diol)	IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 40%	Vaccinia virus
5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole	shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
5-[[3-(dimethylamino)propyl]amino]-3-methylpyrimido[4,5-b]quinoline-2,4(3H,4aH)-dione	IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 70%	Vaccinia virus
7,8-dimethoxy-2-pyridin-4-yl-4H-chromen-4-one	IC90 (compound concentration at which 90% or higher inhibition is observed) 10 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
biphenyl-3,4'-diylbis(arsonic acid)	shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
dibiphenyl-4-yl(hydroxy)acetic acid	IC90 (compound concentration at which 90% or higher inhibition is observed) 1 microM, using high-throughput screen, relaxation inhibition 100%	Vaccinia virus
dihydroxy[4-[(2-hydroxyethyl)sulfamoyl]phenyl]oxoantimonate(2-)	does not inhibit supercoil relaxation at 10 microM concentration. IC90 (compound concentration at which 90% or higher inhibition is observed) 5 microM, using high-throughput screen, relaxation inhibition 0%	Vaccinia virus
additional information	biphenyl-3,4'-diylbis(arsonic acid) and 5-(2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyl-6-[(4-methylphenyl)sulfonyl]tetrahydrofuro[2,3-d][1,3]dioxole show no inhibition even at compound concentrations of 20 microM	Homo sapiens
additional information	using molecular beacon assay for topo I to blindly screen a 1990-member small-molecule library and to identify several specific inhibitors of the poxvirus topoisomerase	Vaccinia virus
N,N,N-trimethyl-1H-pyridazino[4,3-b][1,4]benzothiazin-3-aminium	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
phenazine-2,7-diylbis(arsonic acid)	IC90 (compound concentration at which 90% or higher inhibition is observed) 100 microM, using high-throughput screen, relaxation inhibition 50%	Vaccinia virus
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)	partial or complete inhibition of hTopo is only observed at relatively high compound concentrations in the range 5 to 20 microM	Homo sapiens
[3-[(E)-2-carboxyethenyl]phenyl](dihydroxy)oxoantimonate(2-)	shows significant inhibition of plasmid supercoil relaxation even at 100 nM concentrations. IC90 (compound concentration at which 90% or higher inhibition is observed) 0.1 microM, using high-throughput screen, relaxation inhibition 70%	Vaccinia virus

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Vaccinia virus	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Vaccinia virus

Synonyms

Synonyms	Comment	Organism
DNA topoisomerase	-	Homo sapiens
DNA topoisomerase	-	Vaccinia virus
hTopo	-	Homo sapiens
vTopo	closely related to the human type I topoisomerase (hTopo)	Vaccinia virus