Background:

NSC 207895 is a small-molecule inhibitor of MDMX with GI50 value of 117nM [1].

NSC 207895 is a benzofuroxan derivative and is less toxic. NSC 207895 decreases the activity of MDMX promoter and subsequently decreases both the mRNA and protein levels of MDMX in MCF-7 cells. This inhibition of MDMX is accompanied with the activation of p53. NSC 207895 induces apoptosis in MCF-7 cells since it induces pro-apoptotic gene expression. It is found that the cleavage of PARP is significantly induced by NSC 207895 [2].

NSC 207895 is also found to be a DNA-damaging agent. It shows strong functional interactions with both DNA repair and replication fork complexes. NSC 207895 activates the DNA damage response (DDR) and leads a delay in cell cycle progression [3].

参考文献:
[1] Hawes JJ, Nerva JD, Reilly KM. Novel dual-reporter preclinical screen for antiastrocytoma agents identifies cytostatic and cytotoxic compounds. J Biomol Screen. 2008 Sep;13(8):795-803.
[2] Wang H, Ma X, Ren S, Buolamwini JK, Yan C. A small-molecule inhibitor of MDMX activates p53 and induces apoptosis. Mol Cancer Ther. 2011 Jan;10(1):69-79.
[3] Kapitzky L, Beltrao P, Berens TJ, Gassner N, Zhou C, Wüster A, Wu J, Babu MM, Elledge SJ, Toczyski D, Lokey RS, Krogan NJ. Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action. Mol Syst Biol. 2010 Dec 21;6:451.