Eprenetapopt (APR-246)

Catalog No.S7724 Batch:S772404

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Technical Data

Formula

C10H17NO3
Molecular Weight 199.25 CAS No. 5291-32-7
Solubility (25°C)* In vitro DMSO 40 mg/mL (200.75 mM)
Water 40 mg/mL (200.75 mM)
Ethanol 40 mg/mL (200.75 mM)
In vivo (Add solvents to the product individually and in order)
5% DMSO 95% Corn oil
2.0mg/ml
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.0mg/ml
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
Mutant p53 [2]
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.  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].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    OVCAR-3 cells

  • Concentrations

    40 μM

  • Incubation Time

    20 h

  • Method

    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. 
Animal Study:

[1]
  • Animal Models

    CD-1 Nu/Nu mice

  • Dosages

    400 mg/kg/day

  • Administration

    i.v.

Selleck's Eprenetapopt (APR-246) has been cited by 22 publications

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
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
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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