ME0328

Catalog No.S7438 Batch:S743801

Technical Data

Formula	C₁₉H₁₉N₃O₂
Molecular Weight	321.37	CAS No.	1445251-22-8
Solubility (25°C)*	In vitro	DMSO	64 mg/mL (199.14 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

ME0328 is a potent and selective PARP inhibitor with IC50 of 0.89 μM for PARP3, about 7-fold selectivity over PARP1.

Targets

PARP3 ^[1]	PARP1 ^[1]
0.89 μM	6.3 μM

In vitro

ME0328 is soluble, cell permeable, and metabolically stable in human liver microsomes and rat hepatocytes. ME0328 (10 μM) results in a significant delay of γH2AX-foci resolution by affecting ARTD3 in A549 and MRC5 cells without significant toxicity. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	Enzymatic Assays Protein ADP-ribosylation is measured using hexahistidine-tagged ARTD proteins and recombinant histone proteins captured on 96-well Ni2+-chelating plates (5-PRIME). ADP-ribosylation reactions are initiated by addition of NAD+ (2% biotinylated), and modified reaction products are detected by chemiluminescence. Km values are estimated using plots of initial rates vs. NAD+ concentrations and linear curve fitting with GraphPad Prism. All compounds are dissolved in dimethyl sulfoxide (DMSO) to a stock concentration of 50 mM. Experiments to determine IC50 values are conducted with compound concentrations in the range between 10 nM and 450 μM with a DMSO concentration of 1% (v/v). Measurements are carried out at an NAD+ concentration below Km for each transferase. IC50 values are estimated using curve fitting with GraphPad Prism. Reported values represent means ± SE of the fits of the curves based on duplicate or triplicate experiments, each determined based on three replicates.
Cell Assay:^{^[1]}	Cell lines A549 and MRC5 cells. Concentrations ~10 μM Incubation Time 72 hours Method Compound cytotoxicity in A549 and MRC5 cells is evaluated using WST-1 assays. A549 cells are cultured in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal calf serum (FCS), penicillin, and streptomycin. MRC5 cells are cultured in Minimal Essential Medium supplemented with 10% FCS, penicillin, streptomycin, and l-glutamine. Both cell lines are maintained in a humidified incubator at 37°C and 5% CO₂.

Kinase Assay:^{^[1]}

Enzymatic Assays
Protein ADP-ribosylation is measured using hexahistidine-tagged ARTD proteins and recombinant histone proteins captured on 96-well Ni2+-chelating plates (5-PRIME). ADP-ribosylation reactions are initiated by addition of NAD+ (2% biotinylated), and modified reaction products are detected by chemiluminescence. Km values are estimated using plots of initial rates vs. NAD+ concentrations and linear curve fitting with GraphPad Prism. All compounds are dissolved in dimethyl sulfoxide (DMSO) to a stock concentration of 50 mM. Experiments to determine IC50 values are conducted with compound concentrations in the range between 10 nM and 450 μM with a DMSO concentration of 1% (v/v). Measurements are carried out at an NAD+ concentration below Km for each transferase. IC50 values are estimated using curve fitting with GraphPad Prism. Reported values represent means ± SE of the fits of the curves based on duplicate or triplicate experiments, each determined based on three replicates.

Cell Assay:^{^[1]}

Cell lines
A549 and MRC5 cells.
Concentrations
~10 μM
Incubation Time
72 hours
Method
Compound cytotoxicity in A549 and MRC5 cells is evaluated using WST-1 assays. A549 cells are cultured in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal calf serum (FCS), penicillin, and streptomycin. MRC5 cells are cultured in Minimal Essential Medium supplemented with 10% FCS, penicillin, streptomycin, and l-glutamine. Both cell lines are maintained in a humidified incubator at 37°C and 5% CO₂.

References

[1] Lindgren AE, et al. ACS Chem Biol. 2013, 8(8), 1698-1703.

Customer Product Validation

: Data from [Data independently produced by , , Nat Commun, 2017, 8:15110.]

: Data from [Data independently produced by , , Breast Cancer Res Treat, 2018, 172(1):23-32]

Selleck's ME0328 has been cited by 6 publications

Curcumin sensitizes lymphoma cells to DNA damage agents through regulating Rad51-dependent homologous recombination [Zhao Q Biomed Pharmacother, 2018, 97:115-119]	PubMed: 29080451
Inhibition of Parp1 by BMN673 Effectively Sensitizes Cells to Radiotherapy by Upsetting the Balance of Repair Pathways Processing DNA Double-Strand Breaks [ Mol Cancer Ther, 2018, 17(10):2206-2216]	PubMed: 29970481
PARP3 inhibitors ME0328 and olaparib potentiate vinorelbine sensitization in breast cancer cell lines [Sharif-Askari B Breast Cancer Res Treat, 2018, 172(1):23-32]	PubMed: 30039287
The Development of a Biotinylated NAD+-Applied Human Poly(ADP-Ribose) Polymerase 3 (PARP3) Enzymatic Assay. [ SLAS Discov, 2018, 23(6):545-553]	PubMed: 29676938
PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA. [Day TA, et al. Nat Commun, 2017, 8:15110]	PubMed: 28447610
CRISPR-mediated targeting of HER2 inhibits cell proliferation through a dominant negative mutation [Wang H Cancer Lett, 2017, 385:137-143]	PubMed: 27815036

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.