Literature summary for 3.2.1.143 extracted from

James, D.I.; Smith, K.M.; Jordan, A.M.; Fairweather, E.E.; Griffiths, L.A.; Hamilton, N.S.; Hitchin, J.R.; Hutton, C.P.; Jones, S.; Kelly, P.; McGonagle, A.E.; Small, H.; Stowell, A.I.; Tucker, J.; Waddell, I.D.; Waszkowycz, B.; Ogilvie, D.J.
First-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to Olaparib (2016), ACS Chem. Biol., 11, 3179-3190 .

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Inhibitors

Inhibitors	Comment	Organism	Structure
1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide	-	Homo sapiens
1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide	-	Homo sapiens
additional information	first-in-class chemical probes against poly(ADP-ribose) glycohydrolase (PARG) inhibit DNA repair with differential pharmacology to poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. No inhibition of PARG by 1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-methyl-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide and 1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-methyl-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide. Cytotoxicity measurements of inhibitors with different cell lines	Homo sapiens
N-tert-butyl-9,10-dioxo-9,10-dihydroanthracene-2-sulfonamide	PDD00013907, inhibition of enzyme PARG with the small molecule leads to poly(ADP-ribose) (PAR) chain persistence in intact cells, overview. It shows cellular activity and cytotoxicity in HeLa cells	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
poly(ADP-ribose) + H2O	Homo sapiens	-	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q86W56	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
HCC-1937 cell	-	Homo sapiens	-
HeLa cell	-	Homo sapiens	-
MDA-MB-436 cell	-	Homo sapiens	-
ZR-75-1 cell	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
poly(ADP-ribose) + H2O	-	Homo sapiens	?	-	?
poly(ADP-ribose) + H2O	a commercial Bt-NAD ribosylated PARP1 substrate	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
PARG	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
22	-	assay at room temperature	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.000026	-	pH 7.4, 22°C	Homo sapiens	1-[(1,3-dimethyl-1H-pyrazol-5-yl)methyl]-N-(1-methylcyclopropyl)-3-[(2-methyl-1,3-thiazol-5-yl)methyl]-2,4-dioxo-1,2,3,4-tetrahydroquinazoline-6-sulfonamide
0.00004	-	pH 7.4, 22°C	Homo sapiens	1-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-N-(1-methylcyclopropyl)-2-oxo-3-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1H-benzimidazole-5-sulfonamide
0.06	-	pH 7.4, 22°C	Homo sapiens	N-tert-butyl-9,10-dioxo-9,10-dihydroanthracene-2-sulfonamide

General Information

General Information	Comment	Organism
physiological function	the enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). Critical to this repair process is the orderly degradation of PAR chains. The roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely intertwined	Homo sapiens

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Release 2023.1 (January 2023)