General Information of the Protein
Protein ID
PT03940
Protein Name
Poly(ADP-ribose) glycohydrolase
Gene Name
PARG
Sequence
MNAGPGCEPCTKRPRWGAATTSPAASDARSFPSRQRRVLDPKDAHVQFRVPPSSPACVPGRAGQHRGSATSLVFKQKTITSWMDTKGIKTAESESLDSKENNNTRIESMMSSVQKDNFYQHNVEKLENVSQLSLDKSPTEKSTQYLNQHQTAAMCKWQNEGKHTEQLLESEPQTVTLVPEQFSNANIDRSPQNDDHSDTDSEENRDNQQFLTTVKLANAKQTTEDEQAREAKSHQKCSKSCDPGEDCASCQQDEIDVVPESPLSDVGSEDVGTGPKNDNKLTRQESCLGNSPPFEKESEPESPMDVDNSKNSCQDSEADEETSPGFDEQEDGSSSQTANKPSRFQARDADIEFRKRYSTKGGEVRLHFQFEGGESRTGMNDLNAKLPGNISSLNVECRNSKQHGKKDSKITDHFMRLPKAEDRRKEQWETKHQRTERKIPKYVPPHLSPDKKWLGTPIEEMRRMPRCGIRLPLLRPSANHTVTIRVDLLRAGEVPKPFPTHYKDLWDNKHVKMPCSEQNLYPVEDENGERTAGSRWELIQTALLNKFTRPQNLKDAILKYNVAYSKKWDFTALIDFWDKVLEEAEAQHLYQSILPDMVKIALCLPNICTQPIPLLKQKMNHSITMSQEQIASLLANAFFCTFPRRNAKMKSEYSSYPDINFNRLFEGRSSRKPEKLKTLFCYFRRVTEKKPTGLVTFTRQSLEDFPEWERCEKPLTRLHVTYEGTIEENGQGMLQVDFANRFVGGGVTSAGLVQEEIRFLINPELIISRLFTEVLDHNECLIITGTEQYSEYTGYAETYRWSRSHEDGSERDDWQRRCTEIVAIDALHFRRYLDQFVPEKMRRELNKAYCGFLRPGVSSENLSAVATGNWGCGAFGGDARLKALIQILAAAAAERDVVYFTFGDSELMRDIYSMHIFLTERKLTVGDVYKLLLRYYNEECRNCSTPGPDIKLYPFIYHAVESCAETADHSGQRTGT
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
Function
Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose) (PubMed:15450800, PubMed:21892188, PubMed:23102699, PubMed:23474714, PubMed:33186521, PubMed:34321462, PubMed:34019811). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers (PubMed:23102699, PubMed:23481255). It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated (PubMed:21892188, PubMed:23474714, PubMed:33186521). Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG (PubMed:23102699, PubMed:34019811). Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress (PubMed:24906880). Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond (PubMed:33186521). Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257).
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Uniprot ID
Primary ID:
Q86W56

Secondarily ID:
A5YBK3
B2RC24
B4DIU5
B4DYR4
I6RUV3
Q6E4P6
Q6E4P7
Q7Z742
Q9Y4W7
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Ensembl ID
ENSG00000227345
HGNC ID
HGNC:8605
Subcellular Location
Nucleus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000017 , HeLa
Compound ID Compound Name Compound Formula
CP0243255
US10239843, Example 162
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C23H25N5O4S3
 1
1
EC50 = 9.2 nM
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CP0476897
US10239843, Example 170
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C23H26N6O4S2
 1
1
EC50 = 20 nM
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CP0536296
US10239843, Example 156
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C21H24N4O4S2
 1
1
EC50 = 28 nM
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CP0365220
PDD00017273 (4)
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C23H26N6O4S2
 1
1
EC50 = 37 nM
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CP0164488
US10239843, Example 197
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C21H24N4O5S
 1
1
EC50 = 49 nM
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CP0082747
US10239843, Example 174
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C21H25N5O4S
 1
1
EC50 = 56 nM
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CP0082750
US10239843, Example 198
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C20H20N4O5S
 1
1
EC50 = 76 nM
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CP0197811
US10239843, Example 291
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C19H23N5O4S
 2
1
EC50 = 78 nM
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2
IC50 = 80 nM
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CP0360288
US10239843, Example 161
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C20H20N4O4S2
 1
1
EC50 = 82 nM
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CP0243254
US10239843, Example 173
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C23H27N7O4S
 1
1
EC50 = 88 nM
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CP0082748
US10239843, Example 304
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C19H22N4O5S
 1
1
EC50 = 120 nM
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CP0082752
1-Ethyl-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C18H21N5O4S2
 1
1
EC50 = 120 nM
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CP0230964
US10239843, Example 207
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C23H26N6O5S
 1
1
EC50 = 120 nM
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CP0243253
US10239843, Example 178
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C20H21N5O4S
 1
1
EC50 = 130 nM
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CP0079145
US10239843, Example 39
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C16H17N3O4S
 1
1
EC50 = 250 nM
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CP0168929
US10239843, Example 297
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C21H25N5O5S
 1
1
EC50 = 250 nM
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CP0255486
1-[(2,5-Dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C22H25N7O4S2
 1
1
EC50 = 270 nM
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CP0405435
US10239843, Example 194
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C17H16N4O4S
 1
1
EC50 = 270 nM
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CP0116460
US10239843, Example 305
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C21H24N4O6S
 1
1
EC50 = 280 nM
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CP0230975
US10239843, Example 192
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C20H22N6O4S
 1
1
EC50 = 560 nM
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CP0255478
US10239843, Example 23
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C17H21N3O4S
 1
1
EC50 = 620 nM
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CP0243242
US10239843, Example 4
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C16H21N3O4S
 1
1
EC50 = 1100 nM
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CP0405436
US10239843, Example 193
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C18H20N4O4S
 1
1
EC50 = 1100 nM
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CP0257820
US10239843, Example 2
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C14H17N3O4S
 1
1
EC50 = 1800 nM
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CP0243245
US10239843, Example 8
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C20H21N3O4S
 1
1
EC50 = 2300 nM
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CP0079146
US10239843, Example 34
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C20H27N3O4S
 1
1
EC50 = 2700 nM
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CP0164481
US10239843, Example 9
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C15H19N3O4S
 1
1
EC50 = 3600 nM
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CP0569791
US10239843, Example 5
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C16H18N4O4S
 1
1
EC50 = 5600 nM
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CP0079144
US10239843, Example 25
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C16H21N3O5S
 1
1
EC50 = 6100 nM
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CP0082731
US10239843, Example 26
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C17H24N4O4S
 1
1
EC50 = 6400 nM
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CP0079138
N-(1-methylcyclopropyl)-9,10-dioxoanthracene-2-sulfonamide
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C18H15NO4S
 1
1
EC50 = 6600 nM
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CP0082730
3-Methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
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C13H15N3O4S
 1
1
EC50 = 8100 nM
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CP0243244
US10239843, Example 175
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C15H16N4O4S
 1
1
EC50 = 8900 nM
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CP0458051
US10239843, Example 3
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C14H14N4O4S
 1
1
EC50 = 14000 nM
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CP0079139
N-(1-cyanocyclopropyl)-9,10-dioxoanthracene-2-sulfonamide
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C18H12N2O4S
 1
1
EC50 = 19000 nM
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CP0079137
N-cyclopropyl-9,10-dioxoanthracene-2-sulfonamide
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C17H13NO4S
 1
1
EC50 = 22000 nM
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CP0230129
PDD00013907 (1)
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C18H17NO4S
 1
1
EC50 = 30000 nM
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CP0519217
1-[(1-methylpyrazol-3-yl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-N-[1-(trideuteriomethyl)cyclopropyl]quinazoline-6-sulfonamide
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C22H25N7O4S
 1
1
IC50 = 70 nM
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CP0519215
1-Ethyl-N-[1-(fluoromethyl)cyclopropyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C19H22FN5O4S
 1
1
IC50 = 80 nM
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CP0423252
N-(1-methylcyclopropyl)-1-[(1-methylpyrazol-3-yl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide
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C22H25N7O4S
 1
1
IC50 = 90 nM
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CP0477071
N-[1-(fluoromethyl)cyclopropyl]-1-[(1-methylpyrazol-3-yl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide
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C22H24FN7O4S
 1
1
IC50 = 170 nM
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CP0468991
N-[1-(Fluoromethyl)cyclopropyl]-1-methyl-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C18H20FN5O4S
 1
1
IC50 = 290 nM
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CP0230973
US10239843, Example 155
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C18H21N5O4S
 1
1
IC50 = 330 nM
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CP0423251
N-[1-(difluoromethyl)cyclopropyl]-1-[(1-methylpyrazol-3-yl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide
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C22H23F2N7O4S
 1
1
IC50 = 1250 nM
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CP0468992
1-[(1-methylpyrazol-3-yl)methyl]-3-[(1-methylpyrazol-4-yl)methyl]-2,4-dioxo-N-[1-(trifluoromethyl)cyclopropyl]quinazoline-6-sulfonamide
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C22H22F3N7O4S
 1
1
IC50 = 4100 nM
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CP0477070
1-ethyl-N-[1-(fluoromethyl)cyclopropyl]-3-[(5-methyl-1,2-oxazol-3-yl)methyl]-2,4-dioxoquinazoline-6-sulfonamide
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C19H21FN4O5S
 1
1
IC50 = 6600 nM
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Biochemical Assays
Compound ID Compound Name Compound Formula
CP0243255
US10239843, Example 162
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C23H25N5O4S3
 1
1 EC50 = 4.8 nM
CP0476897
US10239843, Example 170
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C23H26N6O4S2
 1
1 EC50 = 6 nM
CP0536296
US10239843, Example 156
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C21H24N4O4S2
 1
1 EC50 = 19 nM
CP0243254
US10239843, Example 173
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C23H27N7O4S
 1
1 EC50 = 23 nM
CP0365220
PDD00017273 (4)
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C23H26N6O4S2
 1
1 EC50 = 26 nM
CP0082747
US10239843, Example 174
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C21H25N5O4S
 1
1 EC50 = 29 nM
CP0230964
US10239843, Example 207
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C23H26N6O5S
 1
1 EC50 = 38 nM
CP0360288
US10239843, Example 161
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C20H20N4O4S2
 1
1 EC50 = 45 nM
CP0243253
US10239843, Example 178
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C20H21N5O4S
 1
1 EC50 = 52 nM
CP0164488
US10239843, Example 197
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C21H24N4O5S
 1
1 EC50 = 55 nM
CP0255486
1-[(2,5-Dimethylpyrazol-3-yl)methyl]-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C22H25N7O4S2
 1
1 EC50 = 64 nM
CP0168929
US10239843, Example 297
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C21H25N5O5S
 1
1 EC50 = 69 nM
CP0082750
US10239843, Example 198
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C20H20N4O5S
 1
1 EC50 = 100 nM
CP0197811
US10239843, Example 291
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C19H23N5O4S
 1
1 EC50 = 170 nM
CP0082752
1-Ethyl-N-(1-methylcyclopropyl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)methyl]-2,4-dioxo-quinazoline-6-sulfonamide
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C18H21N5O4S2
 1
1 EC50 = 240 nM
CP0405435
US10239843, Example 194
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C17H16N4O4S
 1
1 EC50 = 250 nM
CP0405436
US10239843, Example 193
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C18H20N4O4S
 1
1 EC50 = 270 nM
CP0230975
US10239843, Example 192
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C20H22N6O4S
 1
1 EC50 = 280 nM
CP0082748
US10239843, Example 304
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C19H22N4O5S
 1
1 EC50 = 330 nM
CP0116460
US10239843, Example 305
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C21H24N4O6S
 1
1 EC50 = 340 nM
CP0230973
US10239843, Example 155
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C18H21N5O4S
 1
1 EC50 = 390 nM
CP0255478
US10239843, Example 23
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C17H21N3O4S
 1
1 EC50 = 440 nM
CP0079146
US10239843, Example 34
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C20H27N3O4S
 1
1 EC50 = 560 nM
CP0079145
US10239843, Example 39
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C16H17N3O4S
 1
1 EC50 = 710 nM
CP0079144
US10239843, Example 25
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C16H21N3O5S
 1
1 EC50 = 1100 nM
CP0164481
US10239843, Example 9
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C15H19N3O4S
 1
1 EC50 = 1300 nM
CP0243245
US10239843, Example 8
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C20H21N3O4S
 1
1 EC50 = 1300 nM
CP0243242
US10239843, Example 4
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C16H21N3O4S
 1
1 EC50 = 1500 nM
CP0569791
US10239843, Example 5
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C16H18N4O4S
 1
1 EC50 = 1800 nM
CP0082731
US10239843, Example 26
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C17H24N4O4S
 1
1 EC50 = 2000 nM
CP0243244
US10239843, Example 175
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C15H16N4O4S
 1
1 EC50 = 2800 nM
CP0079139
N-(1-cyanocyclopropyl)-9,10-dioxoanthracene-2-sulfonamide
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C18H12N2O4S
 1
1 EC50 = 3300 nM
CP0257820
US10239843, Example 2
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C14H17N3O4S
 1
1 EC50 = 3900 nM
CP0082730
3-Methyl-N-(1-methylcyclopropyl)-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
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C13H15N3O4S
 1
1 EC50 = 4000 nM
CP0458051
US10239843, Example 3
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C14H14N4O4S
 1
1 EC50 = 5000 nM
CP0079138
N-(1-methylcyclopropyl)-9,10-dioxoanthracene-2-sulfonamide
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C18H15NO4S
 1
1 EC50 = 6000 nM
CP0079137
N-cyclopropyl-9,10-dioxoanthracene-2-sulfonamide
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C17H13NO4S
 1
1 EC50 = 13000 nM
CP0230129
PDD00013907 (1)
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C18H17NO4S
 2
1 EC50 = 81000 nM
2 Kd = 1.45 nM