No problem, biodoc. MDM2 is usually overexpressed in cancers with wild type p53. With continuous exposure to Kevetrin, it’s my understanding that the level of MDM2 in the bloodstream will decrease with phosphorylation, followed by transportation to the nucleus of the cell. Obviously the MOA is very complex so I don’t know exactly how. Hopefully this diagram helps.

http://mcr.aacrjournals.org/content/1/14/1001/F1.large.jpg

http://mcr.aacrjournals.org/content/1/14/1001.full.html

BTW, are you as excited about the planning of the ulcerative proctitis PoC trial as I am?

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sox, thanks for the outstanding explanation. Question, if the genes are turned on and functional p53 proteins are available for a short period of time, and the MDM2 complex is only briefly disrupted, what effect would you anticipate with more prolonged (continuous) exposure to Kevetrin? Perhaps the equivalent of a protective reboot? TIA and sorry for my lack of involvement earlier- long day at work...

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