SJ-172550 is a small molecule inhibitor of MDMX; competes for the wild type p53 peptide binding to MDMX with an EC50 of 5 μM.
The p53 pathway is disrupted in virtually every human tumor. SJ-172550 binds the p53-binding pocket of MDMX, thereby displacing p53. SJ-172550 binds reversibly to MDMX and effectively kills retinoblastoma cells in which the expression of MDMX is amplified. The effect of SJ-172550 is additive when combined with an MDM2 inhibitor nutlin-3a[1]. SJ-172550 acts through a complicated mechanism in which the compound forms a covalent but reversible complex with MDMX and locks MDMX into a conformation that is unable to bind p53. The relative stability of this complex is influenced by many factors including the reducing potential of the media, the presence of aggregates[2].
References:
[1]. Reed D, et al. Identification and characterization of the first small molecule inhibitor of MDMX. J Biol Chem. 2010 Apr 2;285(14):10786-96.
[2]. Bista M, et al. On the mechanism of action of SJ-172550 in inhibiting the interaction of MDM4 and p53. PLoS One. 2012;7(6):e37518.