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MDMXMIPS (Million Instructions Per Second) Digital Media Extensions
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An overabundance of MDMX or its sister protein, MDM2, can promote tumor progression by binding and suppressing a protein called p53.
MDM2 and MDMX use different mechanisms to disrupt the p53 pathway.
Evidence suggests SJ-172550 works by binding in a reversible manner to a pocket in the MDMX molecule.
We went from a discovery in childhood cancer, MDMX amplification, to characterizing this first inhibitor in about three-and one-half years," Dyer said.
Investigators searched for molecules likely to block MDMX activity.
Dyer said the new compound might help researchers studying the biology of MDMX.
The success in knocking out MDMX with nutlin-3 represents the first example of local delivery of a targeted chemotherapy drug for any childhood cancer, Dyer said.
So knocking out MDMX in those cancers might also dramatically reduce tumor size.
Inhibition of MDM2 and MDMX leads to reactivation of the p53 pathway, thereby driving tumor cells to apoptotic death.
It possessed efficient cell penetration, specific high affinity binding to both MDM2 and MDMX and excellent stability, all important drug properties that have propelled the program towards IND-enabling studies.