APR-246 (PRIMA-1MET)
Catalog No.S7724
Molecular Weight(MW): 199.25
APR-246, also known as 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.
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Biological Activity
| Description | APR-246, also known as 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. 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[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]. |
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| Cell Data |
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| 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]. |
Protocol
| Cell Research: |
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Solubility (25°C)
Chemical Information
| Molecular Weight | 199.25 |
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| Formula | C10H17NO3 |
| CAS No. | 5291-32-7 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
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Clinical Trial Information
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|---|
| NCT03745716 | Recruiting | Drug: APR-246 + azacitidine|Drug: Azacitidine | MDS | Aprea Therapeutics AB | January 11 2019 | Phase 3 |
| NCT03391050 | Terminated | Drug: APR-246|Drug: Dabrafenib | Melanoma | Aprea Therapeutics AB|Jules Bordet Institute | January 18 2018 | Phase 1|Phase 2 |
| NCT02999893 | Suspended | Drug: APR-246 | Oesophageal Carcinoma | Peter MacCallum Cancer Centre Australia | April 11 2017 | Phase 1|Phase 2 |
| NCT00900614 | Completed | Drug: APR-246 | Hematologic Neoplasms|Prostatic Neoplasms | Aprea Therapeutics AB | May 2009 | Phase 1 |
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