Siremadlin (HDM201)

製品コードS8606 バッチS860602

印刷

化学情報

Synonyms

NVP-HDM201

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₆H₂₄Cl₂N₆O₄

分子量

555.41

CAS No.

1448867-41-1

Solubility (25°C)*

体外

DMSO

100 mg/mL (180.04 mM)

Ethanol

100 mg/mL (180.04 mM)

Water

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 1 40%PEG300 2 5%Tween80 3 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 PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; 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	1.25mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clear 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	Siremadlin (HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.
in vitro	HDM201 binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the two proteins and leading to the activation of the p53 pathway^[1]. It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. HDM201 exhibits highly selectivity across a panel of cancer cell lines^[2].
in vivo	HDM201 displays desirable pharmacokinetic and pharmacodynamic profiles in animals together with excellent oral bioavailability. Application of the compound using various dosing schedules triggers rapid and sustained activation of p53-dependent pharmacodynamic biomarkers resulting in tumor regression in multiple xenografted models of p53 wild-type human cancers^[2].

製品説明

Siremadlin (HDM201) is a novel, highly potent and selective inhibitor of the p53-Mdm2 interaction with affinity constant for Mdm2 in the picomolar range and a selectivity ratio greater than 10000-fold vs Mdm4.

in vitro

HDM201 binds to the p53 binding-site of the Mdm2 protein, disrupting the interaction of the two proteins and leading to the activation of the p53 pathway^[1].

It induces robust p53-dependent cell cycle arrest and apoptosis in human p53 wild-type tumor cells. HDM201 exhibits highly selectivity across a panel of cancer cell lines^[2].

in vivo

HDM201 displays desirable pharmacokinetic and pharmacodynamic profiles in animals together with excellent oral bioavailability. Application of the compound using various dosing schedules triggers rapid and sustained activation of p53-dependent pharmacodynamic biomarkers resulting in tumor regression in multiple xenografted models of p53 wild-type human cancers^[2].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MES-SA cells
	濃度	60 nM
	反応時間	72 h
	実験の流れ	Cells were treated with the drug for 72 hours.
動物実験	動物モデル	Uveal melanoma PDX models
	投薬量	75 mg/kg
	投与方法	p.o.

参考

[4] Decaudin D, et al. Eur J Cancer. 2020 Feb;126:93-103.

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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：

Helicobacter pylori-induced NAT10 stabilizes MDM2 mRNA via RNA acetylation to facilitate gastric cancer progression [ J Exp Clin Cancer Res, 2023, 42(1):9]	PubMed: 36609449
Primary head and neck cancer cell cultures are susceptible to proliferation of Epstein-Barr virus infected lymphocytes [ BMC Cancer, 2023, 23(1):47]	PubMed: 36639629
p53 Pathway Inactivation Drives SMARCB1-deficient p53-wildtype Epithelioid Sarcoma Onset Indicating Therapeutic Vulnerability Through MDM2 Inhibition [ Mol Cancer Ther, 2022, 21(11):1689-1700]	PubMed: 36099437
Tipping Growth Inhibition into Apoptosis by Combining Treatment with MDM2 and WIP1 Inhibitors in p53WT Uterine Leiomyosarcoma [ Cancers (Basel), 2021, 14(1)14]	PubMed: 35008180
Preclinical Evaluation of Drug Combinations Identifies Co-Inhibition of Bcl-2/XL/W and MDM2 as a Potential Therapy in Uveal Melanoma [ Eur J Cancer, 2020, 126:93-103]	PubMed: 31927215

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。