Nedisertib (M3814)

Catalog No.S8586 Batch:S858603

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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)
Ethanol 8 mg/mL (16.6 mM)
Water Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 2.400mg/ml (4.98mM) Taking the 1 mL working solution as an example, add 50 μL of 48 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Nedisertib (M3814, Peposertib, MSC2490484A) is an orally bioavailable, highly potent and selective inhibitor of DNA activated protein kinase (DNA-PK) with an IC50 of < 3 nM.
Targets
DNA-PK
(Cell-free assay)
3 nM
In vitro

Nedisertib (M3814) potently inhibits DNA-PK catalytic activity and sensitises multiple cancer cell lines to ionising radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells by this compound leads to an increased number of persistent DSBs.
In Vivo

Oral administration of Nedisertib (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 leads to complete tumour regression at nontoxic doses. Inhibition of DNA-PK autophosphorylation in xenograft tumours by this compound results in an an increased number of persistent DSBs.

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 Nedisertib (M3814) is performed at Oncolead. Cell viability is determined with 3 Gy IR, this compound (5 μmol/L–5 nmol/L), and a combination of 3 Gy IR and it (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

  • https://patents.google.com/patent/WO2014183850A1/en
  • https://pubmed.ncbi.nlm.nih.gov/32220971/

Sellecks Nedisertib (M3814) Has Been Cited by 38 Publications

A redefined InDel taxonomy provides insights into mutational signatures [ Nat Genet, 2025, 57(5):1132-1141] PubMed: 40210680
Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors [ Nat Commun, 2025, 16(1):6123] PubMed: 40610421
LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation [ Nat Commun, 2025, 16(1):7812] PubMed: 40841368
Targeting synthetic lethality between non-homologous end joining and radiation in very-high-risk medulloblastoma [ Cell Rep Med, 2025, 6(7):102202] PubMed: 40562042
Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks [ Genome Biol, 2025, 26(1):96] PubMed: 40229905
Rescue of the disease-associated phenotype in CRISPR-corrected hiPSCs as a therapeutic approach for inherited retinal dystrophies [ Mol Ther Nucleic Acids, 2025, 36(1):102482] PubMed: 40083649
Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage [ JCI Insight, 2025, 10(12)e172370] PubMed: 40392611
Extracellular Mitochondria Exacerbate Retinal Pigment Epithelium Degeneration in Diabetic Retinopathy [ Diabetes, 2025, 74(3):409-415] PubMed: 39715576
DDX1 is required for non-spliceosomal splicing of tRNAs but not of XBP1 mRNA [ Commun Biol, 2025, 8(1):92] PubMed: 39833356
DNA-PK inhibition sustains the antitumor innate immune response in small cell lung cancer [ iScience, 2025, 28(3):111943] PubMed: 40034862

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

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.