Nedisertib (M3814)

製品コードS8586 バッチS858606

印刷

化学情報

Chemical Structure Synonyms Peposertib, MSC2490484A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C24H21ClFN5O3
分子量 481.91 CAS No. 1637542-33-6
Solubility (25°C)* 体外 DMSO 96 mg/mL (199.2 mM)
Ethanol 3 mg/mL (6.22 mM)
Water 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 92 cancer cell lines and resting peripheral blood mononuclear cells (PBMCs)
濃度 5 μmol/L–5 nmol/L
反応時間 120 h
実験の流れ

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.
動物実験 動物モデル 7- to 9-week-old female NMRI (nu/nu) mice
投薬量 5 mg/kg, 25 mg/kg, 100 mg/kg
投与方法 Oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。