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Re: Truthbythought post# 44385

Wednesday, 10/23/2013 11:14:34 AM

Wednesday, October 23, 2013 11:14:34 AM

Post# of 403103
Truthbythought - Sorry for the late reply. After posting yesterday I took a long hike and was pretty tired when I got home.

Excellent and difficult question. Journal articles note the complexity of the pro-apoptotic and anti-apoptotic pathways. There are multiple molecular players involved.

Mutant p53 relies on a tumor specific activation of a p53 stabilizing pathway. To quote:

"The identity of this pathway seems to be linked to the Hsp90 chaperone machinery, which is highly and ubiquitously upregulated
specifically in cancer cells... In fact, in tumor cells mutp53 forms stable complexes with Hsp90."

Kevetrin disrupts the stability of the Hsp90 complex. HDAC6 is the positive regulator of the Hsp90 chaperone activity. Kevetrin modulates the expression of HDA6. Inhibition of HDAC6 leads to mutp53 ubiquination("the kiss of death" for a protein) leading to degradation.

There may be other pathways involved too. But this one is shown on the poster presentation on the CTIX site.

It is quite amazing to me that Dr. M was able to pack so much wallop into this small molecule called Kevetrin. He must be driving Roche crazy after all the time and effort they put into this.
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