Eprenetapopt (APR-246)

製品コードS7724 バッチS772404

印刷

化学情報

Synonyms

PRIMA-1MET

Storage
(From the date of receipt)

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

化学式

C₁₀H₁₇NO₃

分子量

199.25

CAS No.

5291-32-7

Solubility (25°C)*

体外

DMSO

40 mg/mL (200.75 mM)

Water

40 mg/mL (200.75 mM)

Ethanol

40 mg/mL (200.75 mM)

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.
	5%DMSO 1 40%PEG300 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。	2.000mg/ml (10.04mM)
	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。	2.000mg/ml (10.04mM)

* <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	Eprenetapopt (APR-246, PRIMA-1MET)は、主に変異型p53に腫瘍抑制機能を回復させ、また様々な種類のがん細胞に細胞死を誘導することが示されている低分子有機化合物です。APR-246はアポトーシスとオートファジーを誘導します。
in vitro	Eprenetapopt (APR-246), also known as PRIMA-1MET, is the first clinical-stage compound that reactivates mutant p53 and induces apoptosis. It is a prodrug that is converted to the active compound methylene quinuclidinone (MQ), a Michael acceptor that binds to cysteine residues in mutant p53 and restores its wild-type conformation. This compound not only reactivates p53 but also decreases intracellular glutathione levels in a dose-dependent manner. It can trigger apoptosis in a p53-independent manner by inducing ROS and endoplasmic reticulum (ER) stress and by inhibiting thioredoxin reductase 1 (TrxR1). It was also reported that APR-246 induces cell death in myeloma cells independently of p53 status by impairing the GSH/ROS balance. PRIMA-1Met/APR-246 efficiently inhibited the growth of the SCLC cell lines expressing mutant p53 in vitro and induced apoptosis, associated with increased fraction of cells with fragmented DNA, caspase-3 activation, PARP cleavage, Bax and Noxa upregulation and Bcl-2 downregulation in the cells.
in vivo	In a Phase I/II clinical dose-finding study on hematological malignancies and prostate cancer, Eprenetapopt (APR-246) showed a good safety profile, and both clinical and p53-dependent biological responses were observed. It is well tolerated in animal studies, and single treatment with this compound inhibits tumor growth by 21% in mice bearing the aggressively growing A2780-CP20 tumor xenografts.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	OVCAR-3 cells
	濃度	40 μM
	反応時間	20 h
	実験の流れ	Eprenetapopt (APR-246) was used in experiments where OVCAR-3 cells were plated at a density of 75 000 cells per well in 3 ml of medium in 12-well plates. After staining, the samples were analyzed by LSRII flow cytometer.
動物実験	動物モデル	CD-1 Nu/Nu mice
	投薬量	400 mg/kg/day
	投与方法	i.v.

参考

https://pubmed.ncbi.nlm.nih.gov/26086967/
https://pubmed.ncbi.nlm.nih.gov/21415220/

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：

Integrated stress response (ISR) activation and apoptosis through HRI kinase by PG3 and other p53 pathway-restoring cancer therapeutics [ Oncotarget, 2024, 15:614-633]	PubMed: 39288289
The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment [ J Cell Mol Med, 2024, 28(9):e18374]	PubMed: 38722288
Arsenic trioxide extends survival of Li-Fraumeni syndrome mimicking mouse [ Cell Death Dis, 2023, 14(11):783]	PubMed: 38030599
LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function [ JCI Insight, 2023, 8(15)e167440]	PubMed: 37440313
Dihydroartemisinin-induced ferroptosis in acute myeloid leukemia: links to iron metabolism and metallothionein [ Cell Death Discov, 2023, 9(1):97]	PubMed: 36928207
TP53 structure-function relationships in metastatic castrate-sensitive prostate cancer and the impact of APR-246 treatment [ Prostate, 2023, 10.1002/pros.24629]	PubMed: 37812042
Discovery of compounds that reactivate p53 mutants in vitro and in vivo [ Cell Chem Biol, 2022, S2451-9456(22)00275-6]	PubMed: 35948006
Effects of the Mutant TP53 Reactivator APR-246 on Therapeutic Sensitivity of Pancreatic Cancer Cells in the Presence and Absence of WT-TP53 [ Cells, 2022, 11(5)794]	PubMed: 35269416
APR-246-The Mutant TP53 Reactivator-Increases the Effectiveness of Berberine and Modified Berberines to Inhibit the Proliferation of Pancreatic Cancer Cells [ Biomolecules, 2022, 12(2)276]	PubMed: 35204775
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258]	PubMed: 35207746

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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