Home Apoptosis p53 activator - Apoptosis related activator - Autophagy activator Eprenetapopt (APR-246) For research use only.

Eprenetapopt (APR-246)

Synonyms: PRIMA-1MET

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.

Eprenetapopt (APR-246) Chemical Structure

Eprenetapopt (APR-246) Chemical Structure

CAS No. 5291-32-7

Purity & Quality Control

Eprenetapopt (APR-246) Related Products

Signaling Pathway

p53 Signaling Pathways

p53 Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NALM-6 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
UoCB-6 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
EU-3 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
MUTZ-5 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
KOPN-8 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
RS4;11 Cell viability assay high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL 31073076
SKBR3 Cell cycle assay 5 µM 2 weeks lapatinib in combination with APR-246 caused a lower level of G1 arrest and an increase in the sub-G1 fraction 30743996
BT549 Cell viability assay IC50=3.1 μM 30196236
MDA-MB-468 Cell viability assay IC50=5 μM 30196236
MDA-MB-231 Cell viability assay IC50=4.1 μM 30196236
HCC1143 Cell viability assay IC50=6.8 μM 30196236
MDA-MB-453 Cell viability assay IC50=0.9 μM 30196236
SKBR3 Cell viability assay IC50=5.1 μM 30196236
UACC812 Cell viability assay IC50=11.3 μM 30196236
MCF7 Cell viability assay IC50=31.1 μM 30196236
MCF10A Cell viability assay IC50=5.2 μM 30196236
UMSCC10A Cell viability assay 0-50 μM 72 h suppressed cell survival and bore a modest effect on the killing of HNSCC cells 29348462
FaDu Cell viability assay 0-50 μM 72 h suppressed cell survival and bore a modest effect on the killing of HNSCC cells 29348462
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Click to View More Cell Line Experimental Data

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
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].
Cell Research 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. 
Experimental Result Images Methods Biomarkers Images PMID
Western blot FL-PARP / Cleaved PARP p-p53 26452133
Growth inhibition assay Cell viability 26452133
In Vivo
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].
Animal Research Animal Models CD-1 Nu/Nu mice
Dosages 400 mg/kg/day
Administration i.v.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04383938 Completed
Bladder Cancer|Gastric Cancer|Non Small Cell Lung Cancer|NSCLC|Urothelial Carcinoma|Advanced Solid Tumor
Aprea Therapeutics
 June 25 2020 Phase 1|Phase 2
NCT04214860 Completed
Myeloid Malignancy
Aprea Therapeutics
 December 13 2019 Phase 1
NCT03391050 Terminated
Melanoma
Aprea Therapeutics|Jules Bordet Institute
 January 18 2018 Phase 1|Phase 2
NCT02999893 Terminated
Oesophageal Carcinoma
Peter MacCallum Cancer Centre Australia
 April 11 2017 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 199.25 Formula

C10H17NO3
CAS No. 5291-32-7 SDF Download Eprenetapopt (APR-246) SDF
Smiles COCC1(C(=O)C2CCN1CC2)CO
Storage (From the date of receipt)

In vitro
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DMSO : 40 mg/mL ( (200.75 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 40 mg/mL

Ethanol : 40 mg/mL


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