Nedisertib (M3814)

Catalog No.S8586 Batch:S858605

Technical Data

Formula	C₂₄H₂₁ClFN₅O₃
Molecular Weight	481.91	CAS No.	1637542-33-6
Solubility (25°C)*	In vitro	DMSO	96 mg/mL (199.2 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 22 publications

Structure of the human TIP60-C histone exchange and acetyltransferase complex [ Nature, 2024, 10.1038/s41586-024-08011-w]	PubMed: 39260417
Proteogenomic insights into the biology and treatment of pan-melanoma [ Cell Discov, 2024, 10(1):78]	PubMed: 39039072
Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor [ Nat Commun, 2024, 15(1):6843]	PubMed: 39122671
Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair [ Nat Commun, 2024, 15(1):2625]	PubMed: 38521763
DNA-PK participates in pre-rRNA biogenesis independent of DNA double-strand break repair [ Nucleic Acids Res, 2024, gkae316]	PubMed: 38682589
HiHo-AID2: boosting homozygous knock-in efficiency enables robust generation of human auxin-inducible degron cells [ Genome Biol, 2024, 25(1):58]	PubMed: 38409044
Cocaine-induced DNA-PK relieves RNAP II pausing by promoting TRIM28 phosphorylation [ bioRxiv, 2024, 2024.08.19.608673]	PubMed: 39229050
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
Mantis: High-throughput 4D imaging and analysis of the molecular and physical architecture of cells [ PNAS Nexus, 2024, 3(9):pgae323]	PubMed: 39282007

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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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