Nedisertib (M3814)

Synonyms: Peposertib, MSC2490484A

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.

Nedisertib (M3814) Chemical Structure

Nedisertib (M3814) Chemical Structure

CAS: 1637542-33-6

Selleck's Nedisertib (M3814) has been cited by 12 publications

Purity & Quality Control

Batch: Purity: 99.12%
99.12

Products often used together with Nedisertib (M3814)

Paclitaxel


Nedisertib and Paclitaxel combination potentiates the anti-tumor effect in non-small cell lung cancer (NSCLC) cell lines, A549/H460/H1703.


Wang M, et al. Acta Pharm Sin B. 2021 Dec;11(12):3935-3949.

Etoposide


Nedisertib and Etoposide combination potentiates the anti-tumor effect in non-small cell lung cancer (NSCLC) cell lines, A549/H460/H1703.


Wang M, et al. Acta Pharm Sin B. 2021 Dec;11(12):3935-3949.

Cisplatin


Nedisertib and Cisplatin plus etoposide demonstrate increased efficacy in the human small-cell lung cancer xenograft model, NCI-H520.


Sirrenberg C, et al. Cancer Res (2017) 77 (13_Supplement): 4183.

L755507


Nedisertib and L755507 significantly contribute to precise gene editing for single-base modifications in Stargardt disease patients.


Siles L, et al. Mol Ther Nucleic Acids. 2023 Mar 3;32:64-79.

Capecitabine


Nedisertib and Capecitabine, in combination with radiotherapy, are in clinical trials in patients with locally advanced rectal cancer.


Dexheimer TS, et al. Cancer Res Commun. 2023 Aug 25;3(8):1648-1661.

Nedisertib (M3814) Related Products

Signaling Pathway

Choose Selective DNA-PK Inhibitors

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
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]

Cell Research 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.

In Vivo
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]

Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04702698 Completed
Healthy
Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany
January 14 2021 Phase 1

Chemical Information & Solubility

Molecular Weight 481.91 Formula

C24H21ClFN5O3

CAS No. 1637542-33-6 SDF --
Smiles COC1=NN=C(C=C1)C(C2=C(C=C(C(=C2)C3=NC=NC4=C3C=CC(=C4)N5CCOCC5)F)Cl)O
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 96 mg/mL ( (199.2 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 2 mg/mL

Water : Insoluble


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In vivo
Batch:

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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