Eprenetapopt

Eprenetapopt (APR-246) is a first-in-class, small molecule that restores wild-type p53 functions in TP53-mutant cells. Eprenetapopt triggers apoptosis in tumor cells. Eprenetapopt also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance.

Product information

CAS Number: 5291-32-7

Molecular Weight: 199.25

Formula: C10H17NO3

Synonym:

APR-246

PRIMA-1Met

Chemical Name: 2-(hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one

Smiles: COCC1(CO)C(=O)C2CCN1CC2

InChiKey: BGBNULCRKBVAKL-UHFFFAOYSA-N

InChi: InChI=1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 100 mg/mL (501.88 mM; Need ultrasonic) H2O : 50 mg/mL (250.94 mM; Need ultrasonic)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Eprenetapopt inhibits both recombinant TrxR1 in vitro and TrxR1 in cells. Cellular TrxR1 activity is inhibited by Eprenetapopt irrespective of p53 status. Eprenetapopt can directly affect cellular redox status via targeting of TrxR1. Several small molecules have been shown to restore wild-type activity to mutant p53, including CP-31398, PRIMA-1 and Eprenetapopt, MIRA, STIMA, PhiKan-083 and NSC319726. PRIMA-1 and its methylated analog Eprenetapopt promote correct folding of mutant p53, induce cell death by apoptosis, and inhibit tumor growth in mice. Eprenetapopt has also been shown to reactivate mutant forms of the p63 and p73 proteins that share high structural homology with p53. Eprenetapopt is a powerful apoptosis-inducing agent. Eprenetapopt can enhance apoptosis in mutant p53 carrying cells, compared to the p53 null parental cells. Most p53 mutants are in complex with Hsp70 proteins. Eprenetapopt treatment increases Hsp70 expression and nucleolar translocation, in parallel with the induction of nucleolar accumulation of mutant p53. Several lines of evidence suggest that Eprenetapopt can also act independently of the p53 status of the cell. It can radiosensitize prostate carcinoma cell lines with mutant or wild type p53 and p53-/- cells as well. Introduction of mutant p53 (p53ser249 or p53gln248) into p53-/- hepatocarcinoma cells increases sensitivity to Eprenetapopt without the induction of p53 target genes.Eprenetapopt regularly induces apoptosis in mutant p53 expressing cells.

References:

1. Peng X, et al. APR-246/PRIMA-1MET inhibits thioredoxin reductase 1 and converts the enzyme to a dedicated NADPH oxidase. Cell Death Dis. 2013 Oct 24;4:e881.
2. Stuber G, et al. PRIMA-1MET induces nucleolar translocation of Epstein-Barr virus-encoded EBNA-5 protein. Mol Cancer. 2009 Mar 26;8:23.
3. Sallman DA, et al. Eprenetapopt (APR-246) and Azacitidine in TP53-Mutant Myelodysplastic Syndromes. J Clin Oncol. 2021;39(14):1584-1594.

Products are for research use only. Not for human use.