| Identification | Back Directory | [Name]
2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one | [CAS]
5291-32-7 | [Synonyms]
APR-246
PRIMA-1MET
APR246;APR 246
PRIMA-1MET(APR-246)
APR-246 (PRIMA-1MET)
PRIMA-1MET
2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one
2-(Hydroxymethyl)-2-(methoxymethyl)-3-quinuclidinone
2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one
1-Azabicyclo[2.2.2]octan-3-one, 2-(hydroxymethyl)-2-(methoxymethyl)-
PRIMA-1MET 2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one 2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one APR-246 | [Molecular Formula]
C10H17NO3 | [MDL Number]
MFCD20620963 | [MOL File]
5291-32-7.mol | [Molecular Weight]
199.25 |
| Chemical Properties | Back Directory | [Melting point ]
115-116 °C | [Boiling point ]
313.8±17.0 °C(Predicted) | [density ]
1.20±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
Soluble in DMSO (up to 20 mg/ml) | [form ]
powder | [pka]
13.99±0.10(Predicted) | [color ]
white to beige | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month. | [InChI]
1S/C10H17NO3/c1-14-7-10(6-12)9(13)8-2-4-11(10)5-3-8/h8,12H,2-7H2,1H3 | [InChIKey]
BGBNULCRKBVAKL-UHFFFAOYSA-N | [SMILES]
N21CCC(CC2)C(=O)C1(COC)CO |
| Safety Data | Back Directory | [WGK Germany ]
WGK 3 | [Storage Class]
11 - Combustible Solids | [Hazard Classifications]
Eye Irrit. 2
Skin Irrit. 2 |
| Hazard Information | Back Directory | [Description]
PRIMA-1MET?(5291-32-7) reactivates mutant p53, an important tumor suppressor gene, in cancer cells.1?It induces p53-dependent mitochondrial apoptosis?via?activation of caspase-2.2?PRIMA-1MET?showed significant antitumor activity in multiple myeloma?via?activation of p733?and had previously been shown to target p53 family members p63 and p734. Tumor cell death by PRIMA-1MET?has been also shown to be caused by glutathione depletion and induced ROS production in a p53 independent manner.5-7?PRIMA-1MET?probably induces tumor cell death by both reactivating mutant p53 and inhibiting cellular thiol-dependent redox systems.8 | [Uses]
2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one is a small molecule that has shown promising preclinical activity in various cancer types. 2-(Hydroxymethyl)-2-(methoxymethyl)quinuclidin-3-one shows antitumor activity in multiple myeloma by induction of p73 and Noxa. | [Biochem/physiol Actions]
PRIMA-1Met, also called APR-246, is converted to methylene quinuclidinone (MQ), a Michael acceptor. It interacts with p53 through the cysteine (Cys) residue. It blocks the thioredoxin reductase (TrxR1) enzyme. It is under clinical investigation and well-studied. PRIMA-1Met effect is tested on breast cancer specific gene expression. | [storage]
Store at +4°C | [References]
1) Bykov?et al.?(2005),?PRIMA-1MET?synergizes with cisplatin to induce tumor cell apoptosis;?Oncogene?24?3484
2) Shen?et al.?(2008),?PRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2; Oncogene?27?6571
3) Saha?et al.?(2013),?PRIMA-1MET/APR-246 displays high antitumor in multiple myeloma by induction of p73 and Noxa; Mol. Cancer Ther.?12?2331
4) Rokaeus?et al.?(2010),?PRIMA-1(MET)/APR-246 targets mutant forms of p53 family members p63 and p73; Oncogene?29?6442
5) Tessoulin?et al.?(2014),?PRIMA-1Met induces myeloma cell death independent of p53 by impairing GSH/ROS balance; Blood?124?1626
6) Liu?et al.?(2017),?Inhibiting the system xc-/glutathione axis selectively targets cancers with mutant-p53 accumulation; Nat. Commun.?28?14844
7) Synnott?et al.?(2018),?The Mutant p53-Targeting Compound APR-246 Induces ROS-modulating Genes in Breast Cancer Cells; Transl. Oncol.?11?1343
8) Haffo?et al.?(2018),?Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246; Oncogene?24?3484 |
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