PRIMA-1MET
Reactivates mutant p53 / PRIMA-1MET 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
Biochemicals & reagents
5291-32-7
APR-246
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
-20°C
TARGET: Transcription factor; Glutathione -- PATHWAY: Redox; Apoptosis inducer; p53; Transcription -- RESEARCH AREA: Cell death -- DISEASE AREA: Cancer