受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H19N7O2.2HCl |
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分子量 | 438.31 | CAS No. | 1234015-54-3 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 14 mg/mL (31.94 mM) | ||||||||
Water | Insoluble | ||||||||||
Ethanol | Insoluble | ||||||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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. |
製品説明 | Prexasertib(LY2606368) is an ATP-competitive CHK1 inhibitor with a Ki value of 0.9 nmol/L. For CHK2 and RSK, its IC50 values are 8 nM and 9 nM respectively in cell-free assay. |
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in vitro | In nonclinical studies, LY2606368 induced DNA damage as measured by replication catastrophe and increases in pH2A.X, a marker of double-stranded DNA breaks[1]. Treatment of cells with LY2606368 results in the rapid appearance of TUNEL and pH2AX-positive double-stranded DNA breaks in the S-phase cell population. In a functional assay, LY2606368 potently abrogated the G2–M checkpoint activated by doxorubicin in p53-deficient HeLa cells with an EC50 of 9 nmol/L. LY2606368 was broadly antiproliferative with IC50 values typically <50 nmol/L in the most sensitive cell lines with a minority of cell lines showing considerable resistance with IC50's >1,000 nmol/L. LY2606368 requires CDC25A and CDK2 to cause DNA damage[2]. |
in vivo | LY2606368 inhibited tumor growth in cancer xenografts as monotherapy and in combination with other agents[1]. In an orthotopic SKOV3 ovarian cancer model, LY2606368 was shown to inhibit the growth of primary tumors and significantly reduce the incidence of metastases and ascites accumulation. LY2606368 also demonstrated efficacy in an SW1990 orthotopic pancreatic cancer model resulting in a 92% inhibition of primary tumor growth and the elimination of metastases to the lymphnode, spleen, and intestine[3]. |
細胞アッセイ | 細胞株 | HeLa cells |
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濃度 | 33 or 100 nmol/L | |
反応時間 | 12 h | |
実験の流れ | HeLa cells were plated onto T25 flasks and allowed to recover for 24 hours. LY2606368 was then added to give final concentrations of 33 or 100 nmol/L. In some experiments, 20μmol/L Z-VAD-FMK was included during the drug treatment. Cells were treated for 12 hours, and during the last 2 hours, colchicine was added to 1 μg/mL. Fixation of nuclei for metaphase spreads was done following the method of Bayani and Squire. Chromosome spreads were done. A 12-μL volume of cell suspension in 3:1 methanol/acetic acid fixative was dropped from a height of 3 cm onto dry glass slides or coverslips. The slides were then heated for 45 seconds on a 43°C metal block, before being removed to allow drying to complete at room temperature. Coverslips were mounted on slides with Vectashield Hard Set mounting medium with DAPI. Slides were examined with a Leica DMR fluorescence microscope and images were captured using a SPOT RT3 Slider camera. |
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動物実験 | 動物モデル | Female CD-1 nu-/nu- mice |
投薬量 | 15 mg/kg | |
投与方法 | s.c. |
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Data from [Data independently produced by , , Mol Cancer Ther, 2018, 17(12):2676-2688]
Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation [ Nat Commun, 2024, 15(1):2089] | PubMed: 38453961 |
Transcriptional Differential Analysis of Nitazoxanide-Mediated Anticanine Parvovirus Effect in F81 Cells [ Viruses, 2024, 16(2)282] | PubMed: 38400057 |
Actionable loss of SLF2 drives B-cell lymphomagenesis and impairs the DNA damage response [ EMBO Mol Med, 2023, e16431.] | PubMed: 37485814 |
Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states [ Cell Death Discov, 2023, 9(1):285] | PubMed: 37542044 |
Combination therapy with WEE1 inhibition and trifluridine/tipiracil against esophageal squamous cell carcinoma [ Cancer Sci, 2023, 10.1111/cas.15966] | PubMed: 37724648 |
Replicative stress in gastroesophageal cancer is associated with chromosomal instability and sensitivity to DNA damage response inhibitors [ iScience, 2023, 10.1016/j.isci.2023.108169] | PubMed: 37965133 |
Identification of therapeutic sensitivities in a spheroid drug combination screen of Neurofibromatosis Type I associated High Grade Gliomas [ PLoS One, 2023, 18(2):e0277315] | PubMed: 36730269 |
CHEK2 signaling is the key regulator of oocyte survival after chemotherapy [ Sci Adv, 2023, 9(42):eadg0898] | PubMed: 37862420 |
Replicative stress in gastroesophageal adenocarcinoma is associated with chromosomal instability and sensitivity to DNA damage response inhibitors [ bioRxiv, 2023, 2023.03.27.534412] | PubMed: 37034740 |
Clinically relevant CHK1 inhibitors abrogate wild-type and Y537S mutant ERα expression and proliferation in luminal primary and metastatic breast cancer cells [ J Exp Clin Cancer Res, 2022, 41(1):141] | PubMed: 35418303 |
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。