Eprenetapopt (APR-246)

製品コードS7724 バッチS772401

印刷

化学情報

Chemical Structure 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 Insoluble
Ethanol 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.

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) is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant p53 and also to induce cell death in various cancer types. APR-246 induces apoptosis and autophagy.
in vitro APR-246 (PRIMA-1MET) is the first clinical-stage compound that reactivates mutant p53 and induces apoptosis. APR-246 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. APR-246 completely restores the cisplatin and doxorubicin sensitivity to p53-mutant drug-resistant ovarian cancer cells. It not only reactivates p53 but also decreases intracellular glutathione levels in a dose-dependent manner. APR-246 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[1]. 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[2].
in vivo APR-246 showed a good safety profile in a Phase I/II clinical dose-finding study on hematological malignancies and prostate cancer and both clinical and p53-dependent biological responses were observed. In animal studies, APR-246 is well tolerated. Single treatment with APR-246 inhibits tumor growth by 21% in mice bearing the aggressively growing A2780-CP20 tumor xenografts[1].

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

OVCAR-3 cells were plated at a density of 75 000 cells per well in 3 ml of medium in 12-well plates. Next day, 2.5 ml medium was removed and cells were treated with cisplatin or APR-246 or in combination for 20 h. Next day, cells were harvested by trypsinization, washed twice and cells were stained with Annexin V and propidium iodine (PI). 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.

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：

LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function [ JCI Insight, 2023, 8(15)e167440] PubMed: 37440313
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
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y] PubMed: 35118583
Establishment of an acquired lorlatinib-resistant cell line of non-small cell lung cancer and its mediated resistance mechanism [ Clin Transl Oncol, 2022, 10.1007/s12094-022-02884-x] PubMed: 35852680

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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