受注:045-509-1970 |
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Synonyms | AZD1775 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C27H32N8O2 |
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分子量 | 500.6 | CAS No. | 955365-80-7 | |
Solubility (25°C)* | 体外 | DMSO | 80 mg/mL (159.8 mM) | |
Ethanol | 10 mg/mL warmed with 50ºC water bath (19.97 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. |
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。 |
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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 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. |
キナーゼアッセイ | In vitro kinase assays | |
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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 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. |
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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 |
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]
Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers [ Science, 2024, 384(6700):eadk0775] | PubMed: 38843331 |
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 |
ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors [ Br J Cancer, 2024, 10.1038/s41416-024-02745-0] | PubMed: 38965423 |
GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer [ Cell Rep, 2024, 43(8):114606] | PubMed: 39120974 |
G2 arrest primes hematopoietic stem cells for megakaryopoiesis [ Cell Rep, 2024, 43(7):114388] | PubMed: 38935497 |
The Golgi checkpoint: Golgi unlinking during G2 is necessary for spindle formation and cytokinesis [ Life Sci Alliance, 2024, 7(5)e202302469] | PubMed: 38479814 |
Afatinib or Bevacizumab in combination with Osimertinib efficiently control tumor development in orthotopic murine models of non-small lung cancer [ PLoS One, 2024, 19(6):e0304914] | PubMed: 38935790 |
Identification of DNA methylation-regulated WEE1 with potential implications in prognosis and immunotherapy for low-grade glioma [ Cancer Biomark, 2024, 40(3-4):297-317] | PubMed: 39213054 |
Hyperactivation of p53 contributes to mitotic catastrophe in podocytes through regulation of the Wee1/CDK1/cyclin B1 axis [ Ren Fail, 2024, 46(2):2365408] | PubMed: 38874119 |
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。
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