4-[[4,5-Bis(4-chlorophenyl)-4,5-dihydro-2-[4-methoxy-2-(1-methylethoxy)phenyl]-1H-imidazol-1-yl]carbonyl]-2-piperazinone

Uses

(Rac)-Nutlin-3 (Rebemadlin), an active enantiomer of Nutlin-3, is a potent murine double minute (MDM2) inhibitor (IC50=90 nM). (Rac)-Nutlin-3 inhibits MDM2-p53interactions and stabilizes the p53 protein, and induces cell autophagy and apoptosis. (Rac)-Nutlin-3 has the potential for the study of TP53wild-type ovarian carcinomas[1][2].

Definition

ChEBI: 4-[[4,5-bis(4-chlorophenyl)-2-(4-methoxy-2-propan-2-yloxyphenyl)-4,5-dihydroimidazol-1-yl]-oxomethyl]-2-piperazinone is a stilbenoid.

Biological Activity

nutlin-3, a tetra-substituted imidazoline, is a potent and selective small-molecule antagonist of murine double minute 2 (mdm2), which occupies the binding site of p53 in mdm2 and consequently prevent mdm2 binding to p53 leading to the disruption of the autoregulator feedback loop and the fostering of the p53 tumor suppressor network. it also binds to murine double minute 4 (mdm4), which is another component of the p35 tumor surveillance pathway. nutlin-3 is being investigated as an antitumor agent for its antiangiogenic activity in cells through inhibiting endothelial cell migration, inducing cell cycle arrest, and increasing apoptotic tendency in endothelial cells.bernd r. binder. a novel application for murine double minute 2 antagonists: the p53 tumor suppressor network also controls angiogenesis. circ res. 2007; 100: 13-14

in vivo

target

Mdm2

References

[1] Crane EK, et al. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas. PLoS One. 2015 Aug 6;10(8):e0135101. DOI:10.1371/journal.pone.0135101
[2] Tovar C, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1888-93. DOI:10.1073/pnas.0507493103
[3] M Ulrich, et al. Murine tumor models for the in vivo evaluation of natural compounds and their derivatives as new cancer therapeutics. München. 2016.