PRIMA-1Met

5291-32-7

C10H17NO3

H2O : 50 mg/mL (250.94 mM; Need ultrasonic)

Apoptosis; Autophagy; Apoptosis

PRIMA-1Met restores wild-type conformation and function to mutant p53, and triggers apoptosis in tumor cells. PRIMA-1Met also targets the selenoprotein thioredoxin reductase 1 (TrxR1), a key regulator of cellular redox balance. IC50 & Target: p53 activator^[1]
TrxR1 inhibitor^[1] In Vitro: PRIMA-1Met inhibits both recombinant TrxR1 in vitro and TrxR1 in cells. Cellular TrxR1 activity is inhibited by PRIMA-1Met irrespective of p53 status. PRIMA-1Met can directly affect cellular redox status via targeting of TrxR1. Several small molecules have been shown to restore wild-type activity to mutant p53, including CP-31398, PRIMA-1 and PRIMA-1MET, MIRA, STIMA, PhiKan-083 and NSC319726. PRIMA-1 and its methylated analog PRIMA-1Met promote correct folding of mutant p53, induce cell death by apoptosis, and inhibit tumor growth in mice. PRIMA-1Met has also been shown to reactivate mutant forms of the p63 and p73 proteins that share high structural homology with p53^[1]. PRIMA-1MET is a powerful apoptosis-inducing agent. PRIMA-1MET can enhance apoptosis in mutant p53 carrying cells, compared to the p53 null parental cells. Most p53 mutants are in complex with Hsp70 proteins. PRIMA-1MET treatment increases Hsp70 expression and nucleolar translocation, in parallel with the induction of nucleolar accumulation of mutant p53. Several lines of evidence suggest that PRIMA-1MET can also act independently of the p53 status of the cell. It can radiosensitize prostate carcinoma cell lines with mutant or wild type p53 and p53^-/- cells as well. Introduction of mutant p53 (p53ser249 or p53gln248) into p53^-/- hepatocarcinoma cells increases sensitivity to PRIMA-1MET without the induction of p53 target genes. PRIMA-1MET regularly induces apoptosis in mutant p53 expressing cells^[2].