Adavosertib (MK-1775)

製品コードS1525 バッチS152508

印刷

化学情報

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)

Ethanol (warmed with 50ºC water bath)

10 mg/mL (19.97 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG 300 2 5%Tween80 3 50% ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	12.000mg/ml (23.97mM)	Taking the 1 mL working solution as an example, add 50 μL of 240 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.
Clear solution	5%DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	6.000mg/ml (11.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 120 mg/mL clarified DMSO stock solution to 950 μL of corn oil and mix evenly. 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	Adavosertib (MK-1775) inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, it 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, this compound 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. Its treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas at 300 nM, sufficient to inhibit Wee1 by >80%, it displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells. ^[1]
in vivo	Adavosertib (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. Its antitumor efficacy 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
キナーゼアッセイ	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 Adavosertib (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	After cells are treated for 24 hours, Adavosertib (MK-1775) is added for an additional 24 hours. Cell viability is determined with a WST-8 kit using SpectraMax, and 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

参考

https://pubmed.ncbi.nlm.nih.gov/19887545/

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：

KEAP1 and STK11/LKB1 alterations enhance vulnerability to ATR inhibition in KRAS mutant non-small cell lung cancer [ Cancer Cell, 2025, 43(8):1530-1548.e9]	PubMed: 40645185
Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer [ Nat Cancer, 2025, 10.1038/s43018-025-00960-z]	PubMed: 40301653
A patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8]	PubMed: 40147445
SETD2 loss-of-function uniquely sensitizes cells to epigenetic targeting of NSD1-directed H3K36 methylation [ Genome Biol, 2025, 26(1):22]	PubMed: 39910618
Cytoplasmic WEE1 promotes resistance to PD-1 blockade through hyperactivation of the HSP90A/TCL1/AKT signaling axis in NANOGhigh tumors [ Cancer Immunol Res, 2025, 10.1158/2326-6066.CIR-24-0379]	PubMed: 40067354
Geometric deep learning and multiple-instance learning for 3D cell-shape profiling [ Cell Syst, 2025, 16(3):101229]	PubMed: 40112779
WEE1 inhibitor exerts synergistic effect with KRAS G12C inhibitor via MYBL2-RRM2 axis in KRASG12C-mutant lung cancer [ Cell Death Dis, 2025, 16(1):661]	PubMed: 40885709
Versatile enhancement of the killing potential of anti-cancer agents achieved by peptide mimetics of the PCNA interface towards specialized DNA polymerases [ Cell Death Dis, 2025, 16(1):503]	PubMed: 40628724
Targeting Chk1 and Wee1 kinases enhances radiosensitivity of 2D and 3D head and neck cancer models to X-rays and low/high-LET protons [ Cell Death Dis, 2025, 16(1):128]	PubMed: 39994186
Cyclin E1 overexpression sensitizes ovarian cancer cells to WEE1 and PLK1 inhibition [ Oncogene, 2025, 10.1038/s41388-025-03312-4]	PubMed: 39994376

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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