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Eprenetapopt (APR-246)

Name: Eprenetapopt (APR-246)
Brand: Selleck Chemicals
SKU: S7724
Rating: 5 (20 reviews)

Synonyms: PRIMA-1MET

Catalog No.S7724 Purity:99.69%

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

CAS No. 5291-32-7

Purity & Quality Control

Batch: Purity: 99.69%

99.69

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Signaling Pathway

p53 Signaling Pathway

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	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

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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

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

Water : 40 mg/mL

Ethanol : 40 mg/mL

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.				In vivo Formulation Calculator
Clear solution	saline	40.000mg/ml (200.75mM)	Taking the 1 mL working solution as an example, add 40 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
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.
Clear solution	saline	40.000mg/ml (200.75mM)	Taking the 1 mL working solution as an example, add 40 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
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 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.000mg/ml (10.04mM)
	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	2.000mg/ml (10.04mM)
Clear solution	saline	40.000mg/ml (200.75mM)	Taking the 1 mL working solution as an example, add 40 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
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.
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.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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