JA2131 is a small molecule inhibitor with an IC50 of 0.4 μM that specifically targets polyADP-ribose hydrolase (PARG). Replication fork stalling and cancer cell death are caused by JA2131's regulation of the DNA damage response.

Physicochemical Properties

Molecular Formula	C13H19N5O2S2
Molecular Weight	341.45
Exact Mass	341.098
CAS #	6505-99-3
PubChem CID	4361023
Appearance	White to off-white solid powder
Density	1.48g/cm3
Boiling Point	562.5ºC at 760 mmHg
Flash Point	294ºC
Index of Refraction	1.704
LogP	0.691
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	22
Complexity	446
Defined Atom Stereocenter Count	0
InChi Key	XHNSOGDMSSHQFY-UHFFFAOYSA-N
InChi Code	InChI=1S/C13H19N5O2S2/c1-16-10-9(11(21)17(2)13(16)19)14-12(15-10)22-8-5-18-3-6-20-7-4-18/h3-8H2,1-2H3,(H,14,15)
Chemical Name	1,3-dimethyl-8-(2-morpholin-4-ylethylsulfanyl)-6-sulfanylidene-7H-purin-2-one
Synonyms	JA2131
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In PC3 cells, JA2131 (10 mM; 1-2 h) causes hyperPARylation of PARP1[1]. At 10 μM for two weeks, JA2131 suppresses MCF-7, PC3, and MDA-MB-231 cell colony formation. At 0.1 μM-1 mM for seventy-two hours, it exhibits cytotoxicity, inhibiting MRC-50 cells with an IC50 value of 132 μM[1]. The viability of PC3 and A172 glioblastoma cells is inhibited by JA2131 (5 μM; 72 h)[1]. In HeLa cells, JA2131 (10 μM; 2 h) may be acting at the replication fork[1].
Cell Assay	Cell Viability Assay[1] Cell Types: PC3, and A172 glioblastoma cells Tested Concentrations: 0.1 μM-10 mM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited cell viability with IC50s of 33.05 μM (PC3 cells) and 55.34 μM (A172 cells), respectively.
References	[1]. Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nat Commun. 2019 Dec 11;10(1):5654. [2]. Targeting SARS-CoV-2 Nsp3 macrodomain structure with insights from human poly(ADP-ribose) glycohydrolase (PARG) structures with inhibitors. Prog Biophys Mol Biol. 2021 Aug;163:171-186.

Solubility Data

Solubility (In Vitro)

DMSO : ~12.5 mg/mL (~36.6 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (3.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.9287 mL	14.6434 mL	29.2869 mL
	5 mM	0.5857 mL	2.9287 mL	5.8574 mL
	10 mM	0.2929 mL	1.4643 mL	2.9287 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.