ChemicalBook Product Catalog Biochemical Engineering Biochemical Reagents Agonist Inhibitors 2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one

2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one

Product Name2-(Hydroxymethyl)-2-(methoxymethyl)-1-azabicyclo[2.2.2]octan-3-one
CAS5291-32-7
MFC10H17NO3
MW199.25
EINECS
MOL File5291-32-7.mol

Chemical Properties

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 Information

WGK Germany	WGK 3
Storage Class	11 - Combustible Solids
Hazard Classifications	Eye Irrit. 2 Skin Irrit. 2

Usage And Synthesis

Description

PRIMA-1MET(5291-32-7) reactivates mutant p53, an important tumor suppressor gene, in cancer cells.1It induces p53-dependent mitochondrial apoptosisviaactivation of caspase-2.2PRIMA-1METshowed significant antitumor activity in multiple myelomaviaactivation of p733and had previously been shown to target p53 family members p63 and p734. Tumor cell death by PRIMA-1METhas been also shown to be caused by glutathione depletion and induced ROS production in a p53 independent manner.5-7PRIMA-1METprobably 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] VLADIMIR J N BYKOV. PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis[J]. Oncogene, 2005, 24 21: 3484-3491. DOI:10.1038/sj.onc.1208419
[2] J SHEN. PRIMA-1MET induces mitochondrial apoptosis through activation of caspase-2[J]. Oncogene, 2008, 27 51: 6571-6580. DOI:10.1038/onc.2008.249
[3] MANUJENDRA N SAHA. PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa.[J]. Molecular Cancer Therapeutics, 2013: 2331-2341. DOI:10.1158/1535-7163.mct-12-1166
[4] N RÖKAEUS. PRIMA-1MET/APR-246 targets mutant forms of p53 family members p63 and p73[J]. Oncogene, 2010, 29 49: 6442-6451. DOI:10.1038/onc.2010.382
[5] BENOÎT TESSOULIN. PRIMA-1Met induces myeloma cell death independent of p53 by impairing the GSH/ROS balance.[J]. Blood, 2014, 124 10: 1626-1636. DOI:10.1182/blood-2014-01-548800
[6] DAVID S LIU. Inhibiting the system xC-/glutathione axis selectively targets cancers with mutant-p53 accumulation.[J]. Nature Communications, 2017: 14844. DOI:10.1038/ncomms14844
[7] NAOISE C. SYNNOTT . The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells[J]. Translational Oncology, 2018, 11 6: Pages 1343-1349. DOI:10.1016/j.tranon.2018.08.009
[8] LENA HAFFO. Inhibition of the glutaredoxin and thioredoxin systems and ribonucleotide reductase by mutant p53-targeting compound APR-246.[J]. Scientific Reports, 2018: 12671. DOI:10.1038/s41598-018-31048-7

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