Adavosertib (MK-1775)

製品コードS1525 バッチS152510

印刷

化学情報

Chemical Structure Synonyms AZD1775 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C27H32N8O2
分子量 500.6 CAS No. 955365-80-7
Solubility (25°C)* 体外 DMSO 100 mg/mL (199.76 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）
Clear solution
5%DMSO 40%PEG 300 5%Tween80 50% ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/mL clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify; add 50 μL of Tween-80 to the above system, mix evenly to clarify; Then continue to add 500 μL 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 アダボセルチブ (Adavosertib (MK-1775、AZD1775)) は、無細胞アッセイで IC50 が 5.2 nM の強力かつ選択的な Wee1 阻害剤です。G2 DNA 損傷チェックポイントを阻害します。臨床フェーズ2。
in vitro MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells. [1]
in vivo MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models is also moderate. [1]
特徴 The first reported Wee1 inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ In vitro kinase assays
Recombinant human Wee1 is used. Kinase reaction is conducted with 10 μM ATP, 1.0 μCi of [γ-33P]ATP, and 2.5 μg of poly(Lys, Tyr) as a substrate in the presence of increasing concentrations of MK-1775 at 30°C for 30 minutes. Radioactivity incorporated into the substrate is trapped on MultiScreen-PH plates and is counted on a liquid scintillation counter.
細胞アッセイ 細胞株 WiDr, NCI-H1299, TOV21G, and HeLa
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 24 hours
実験の流れ

Cells are treated with or without gemcitabine for 24 hours, then with MK-1775 for an additional 24 hours. Cell viability is determined with a WST-8 kit using SpectraMax. Cellular caspase-3/7 activities are determined with a Caspase-3/7 Glo kit.
動物実験 動物モデル Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors
投薬量 ~20 mg/kg/day
投与方法 Orally

カスタマーフィードバック

Data from [Data independently produced by J Hematol Oncol, 2014, 7:53]

Data from [Data independently produced by Oncol Rep, 2014, 32(5), 1991-8]

Data from [Data independently produced by Endocrinology, 2013, 154(9), 3219-27]

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：

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
ATR limits Rad18-mediated PCNA monoubiquitination to preserve replication fork and telomerase-independent telomere stability [ EMBO J, 2024, 43(7):1301-1324] PubMed: 38467834
The Golgi checkpoint: Golgi unlinking during G2 is necessary for spindle formation and cytokinesis [ Life Sci Alliance, 2024, 7(5)e202302469] PubMed: 38479814
The SUMO-NIP45 pathway processes toxic DNA catenanes to prevent mitotic failure [ Nat Struct Mol Biol, 2023, 10.1038/s41594-023-01045-0] PubMed: 37474739
Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer [ Nat Commun, 2023, 14(1):6332] PubMed: 37816716
Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088] PubMed: 37773176
Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma [ EMBO Mol Med, 2023, e16863.] PubMed: 36779660
SOX2 expression in prostate cancer drives resistance to nuclear hormone receptor signaling inhibition through the WEE1/CDK1 signaling axis [ Cancer Lett, 2023, 565:216209] PubMed: 37169162
Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth [ Cell Death Dis, 2023, 10.1038/s41419-023-06167-3] PubMed: 37758718
Targeted inhibition of the methyltransferase SETD8 synergizes with the Wee1 inhibitor adavosertib in restraining glioblastoma growth [ Cell Death Dis, 2023, 14(9):638] PubMed: 37758718

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。