SCR7 pyrazine is a DNA ligase IV (DNA ligase IV) inhibitor that blocks nonhomologous end joining (NHEJ) in a ligase IV-dependent manner. SCR7 pyrazine is also a CRISPR/Cas9 enhancer that can improve the efficiency of Cas9-mediated homology-directed repair (HDR). SCR7 pyrazine causes apoptosis and has anti-cancer effect.

Physicochemical Properties

Molecular Formula	C18H12N4OS
Molecular Weight	332.38
Exact Mass	332.073
Elemental Analysis	C, 65.05; H, 3.64; N, 16.86; O, 4.81; S, 9.65
CAS #	14892-97-8
Related CAS #	14892-97-8
PubChem CID	10688007
Appearance	Light yellow to yellow solid powder
Melting Point	209 °C
LogP	3.748
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	24
Complexity	487
Defined Atom Stereocenter Count	0
SMILES	S=C1N([H])C(C2=C(N1[H])N=C(C1C([H])=C([H])C([H])=C([H])C=1[H])C(C1C([H])=C([H])C([H])=C([H])C=1[H])=N2)=O
InChi Key	GSRTWXVBHGOUBU-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H12N4OS/c23-17-15-16(21-18(24)22-17)20-14(12-9-5-2-6-10-12)13(19-15)11-7-3-1-4-8-11/h1-10H,(H2,20,21,22,23,24)
Chemical Name	6,7-diphenyl-2-sulfanylidene-1H-pteridin-4-one
Synonyms	SCR-7 pyrazine; SCR7 pyrazine; SCR 7 pyrazine
HS Tariff Code	2933598000
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

Targets	DNA Ligase IV; CRISPR/Cas9
ln Vitro	SCR7 pyrazine (20-100 μM; 24 hours; MCF7 cells) treatment causes unrepaired double-strand breaks (DSBs) to accumulate in cells by interfering with NHEJ[1]. SCR7 pyrazine treatment results in a dose-dependent reduction in cell proliferation, with IC50 values for MCF7, A549, HeLa, T47D, A2780, HT1080, and Nalm6 cells, respectively, of 40 μM, 34 μM, 44 μM, 8.5 μM, 120 μM, 10 μM, and 50 μM[1]. SCR7 pyrazine (20, 40 μM) treatment of MCF7 cells results in increased phosphorylation of ATM and activates p53, while decreasing MDM2, BCL2, and activating proapoptotic proteins, PUMA and BAX. Furthermore, there is a dose-dependent increase in the cleavage of the shorter fragments of MCL1, PARP1, Caspase 3, and Caspase 9[1].
ln Vivo	SCR7 pyrazine (10 mg/kg; intraperitoneal injection; six doses; BALB/c mice) treatment lengthens life expectancy and significantly reduces tumors caused by breast adenocarcinoma[1].
Cell Assay	Cell Line: MCF7 cells Concentration: 20 μM, 40 μM, 100 μM Incubation Time: 24 hours Result: Showed an increase in levels of gH2AX foci and protein.
Animal Protocol	BALB/c mice injected with breast adenocarcinoma cells 10 mg/kg Intraperitoneal injection; on alternate days (0, 2, 4, 6, 8, and 10)
References	[1]. An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression. Cell. 2012 Dec 21;151(7):1474-87. [2]. Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1 Virus in Human Cells. Sci Rep. 2016 Oct 7;6:34531.

Solubility Data

Solubility (In Vitro)

DMSO: ~66 mg/mL (~198.6 mM) Ethanol: ~23 mg/mL (~69.2 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.0086 mL	15.0430 mL	30.0860 mL
	5 mM	0.6017 mL	3.0086 mL	6.0172 mL
	10 mM	0.3009 mL	1.5043 mL	3.0086 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.