Nedisertib (M3814)

Catalog No.S8586 Batch:S858602

Technical Data

Formula	C₂₄H₂₁ClFN₅O₃
Molecular Weight	481.91	CAS No.	1637542-33-6
Solubility (25°C)*	In vitro	DMSO	48 mg/mL (99.6 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.)

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Biological Activity

Description

Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with IC50 of < 3 nM.

Targets

DNA-PK ^[1]
(Cell-free assay)

3 nM

In vitro

M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells leads to an increased number of persistent DSBs.^[2]

In vivo

Inhibition of DNA-PK autophosphorylation in xenograft tumors leads to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiates the antitumor activity of IR and lead to complete tumor regression at nontoxic doses.^[2]

Protocol (from reference)

Cell Assay:^{^[2]}	Cell lines 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs) Concentrations 5 μmol/L–5 nmol/L Incubation Time 120 h Method Radiosensitization of 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs) by M3814 is performed at Oncolead. Cell viability is determined with 3 Gy IR, M3814 (5 μmol/L–5 nmol/L), and a combination of 3 Gy IR and M3814 (5 μmol/L–5 nmol/L). Treated cells are incubated for 120 hours, fixed, stained with sulforhodamine B, and quantified colorimetrically.
Animal Study:^{^[2]}	Animal Models 7- to 9-week-old female NMRI (nu/nu) mice Dosages 5 mg/kg, 25 mg/kg, 100 mg/kg Administration Oral gavage

Cell Assay:^{^[2]}

Cell lines
92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs)
Concentrations
5 μmol/L–5 nmol/L
Incubation Time
120 h
Method
Radiosensitization of 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs) by M3814 is performed at Oncolead. Cell viability is determined with 3 Gy IR, M3814 (5 μmol/L–5 nmol/L), and a combination of 3 Gy IR and M3814 (5 μmol/L–5 nmol/L). Treated cells are incubated for 120 hours, fixed, stained with sulforhodamine B, and quantified colorimetrically.

Animal Study:^{^[2]}

Animal Models
7- to 9-week-old female NMRI (nu/nu) mice
Dosages
5 mg/kg, 25 mg/kg, 100 mg/kg
Administration
Oral gavage

References

Selleck's Nedisertib (M3814) has been cited by 14 publications

HiHo-AID2: boosting homozygous knock-in efficiency enables robust generation of human auxin-inducible degron cells [ Genome Biol, 2024, 25(1):58]	PubMed: 38409044
Identification of the main barriers to Ku accumulation in chromatin [ bioRxiv, 2024, 2024.01.03.574002]	PubMed: 38260538
Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation [ bioRxiv, 2024, 2024.03.08.584115]	PubMed: 38559033
Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing [ Nat Commun, 2023, 14(1):4761]	PubMed: 37580318
Efficient correction of ABCA4 variants by CRISPR-Cas9 in hiPSCs derived from Stargardt disease patients [ Mol Ther Nucleic Acids, 2023, 32:64-79]	PubMed: 36969552
Fanconi anemia-associated chromosomal radial formation is dependent on POLθ-mediated alternative end joining [ Cell Rep, 2023, 42(5):112428]	PubMed: 37086407
Perturbations in 3D genome organization can promote acquired drug resistance [ Cell Rep, 2023, 42(10):113124]	PubMed: 37733591
Ribosome biosynthesis and Hedgehog activity are cooperative actionable signaling mechanisms in breast cancer following radiotherapy [ NPJ Precis Oncol, 2023, 7(1):61]	PubMed: 37380890
Ribosome biosynthesis and Hedgehog activity are cooperative actionable signaling mechanisms in breast cancer following radiotherapy [ NPJ Precis Oncol, 2023, 7(1):61]	PubMed: 37380890
High-Efficiency CRISPR/Cas9-Mediated Correction of a Homozygous Mutation in Achromatopsia-Patient-Derived iPSCs [ Int J Mol Sci, 2023, 24(4)3655]	PubMed: 36835061

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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.

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