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Catalog:
SLK-S7724
Brand:
Selleck
CAS:
5291-32-7
Overview
MDL
-
Molecular Weight
199.25
Molecular Formula
C10H17NO3
SMILES
C(OC)C1(CO)N2CCC(C1=O)CC2
For research use only.
Storage
3 years,-20°C,powder 1 years,-80°C,in solvent
Shipping
Room temperature shipping(Stability testing shows this product can be shipped without any cooling measures.)
Preparing Stock Solutions
1 mg
5 mg
10 mg
1 mM
5.0188 mL
25.0941 mL
50.1882 mL
5 mM
1.0038 mL
5.0188 mL
10.0376 mL
10 mM
0.5019 mL
2.5094 mL
5.0188 mL
50 mM
0.1004 mL
0.5019 mL
1.0038 mL
Description
Eprenetapopt (APR-246, PRIMA-1MET) is a small organic molecule that has been shown to restore tumour-suppressor function primarily to mutant and also to induce cell death in various cancer types. APR-246 induces and .
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. 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.
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.
