Innovation Pharmaceuticals Inc (IPIX)

[KMBJN]

Very puzzling about kevetrin down-regulating p53 in wt-p53 AML lines when the story is that kevetrin is supposed to (re)activate wt-p53 - via phosphorylation of p53 into a form with more stable tetramers ("active" form of p53 with P at S15, that doesn't interact with MDM2 as much) and also phosphorylation of MDM2 to hinder the inactivation of p53 (preventing its ubiquitination and eventual proteasomal degradation) - I believe, from the ASCO 2013 poster summary:



I don't understand this from today's abstract, regarding wt-p53:

In accordance with p53 activity, we observed a great up-regulation of p21

p53 is a transcription factor that when activated is supposed to increase transcription of p21 and PUMA. How can you have a decrease in p53 in wt-p53 cells, then an increase in p21? Their finding is NOT "in accordance," since they had decreased p53 and increased p21. I guess that just goes to the p53-independent pathway you speak of.

Always more to it than expected.

I hope that kevetrin is more than just an HDAC6 inhibitor (and HSP90 inhibitor that leads to breakdown of p53 in both wt and mutated p53 cancer).

Looking forward to hearing more about the p53-independent pathways of kevetrin. Perhaps they can focus more on HSP90 (and other molecular chaperones and co-chaperones) and HDAC inhibitor MOA of kevetrin. HSP90 can stabilize other oncogenes besides mutant p53.

It still isn't clear what kevetrin is doing in wt-p53. We shall see. It's always good to have more clues to the puzzle.