For research use only.
Catalog No.S7724 Synonyms: PRIMA-1MET
CAS No. 5291-32-7
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.
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|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.|
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.|
|In vitro||DMSO||40 mg/mL (200.75 mM)|
|Water||40 mg/mL (200.75 mM)|
* 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.
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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|% DMSO % % Tween 80 % ddH2O|
Working concentration： mg/ml；
Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL，)
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.
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Molecular Weight Calculator
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Clinical Trial Information
|NCT Number||Recruitment||interventions||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT04383938||Recruiting||Drug: APR-246 (eprenetapopt) + Pembrolizumab||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||Recruiting||Drug: APR-246|Drug: Venetoclax|Drug: Azacitidine||Myeloid Malignancy||Aprea Therapeutics||December 13 2019||Phase 1|
|NCT03745716||Active not recruiting||Drug: APR-246 + azacitidine|Drug: Azacitidine||MDS||Aprea Therapeutics||January 11 2019||Phase 3|
|NCT03391050||Terminated||Drug: APR-246|Drug: Dabrafenib||Melanoma||Aprea Therapeutics|Jules Bordet Institute||January 18 2018||Phase 1|Phase 2|
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.
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