Innovation Pharmaceuticals Inc (IPIX)

[Truthbythought]

Thanks. Have traveled down the rabbit hole a bit more based on the info you provided. Some interesting notes.

Hsp90 is a longstanding target of anti-cancer drugs and it has been shown that down regulation of this protein strongly deactivates mutant p53 and upregulates normal p53.

There was actually a drug called Geldanamycin that did just that by inhibiting Hsp90, but unfortunately it had the draw back of liver toxicity. Certain analogues of the drug were being studied as late as 2010 by Bristol-Myers Squibb and studies may even be ongoing - someone contested the end of the trials on wikipedia.

"GA downregulated overexpressed mutant p53 protein (an oncogene) and upregulated wild-type (wt) p53 (a tumour suppressor). The upregulation of wt p53 by GA was independent of ATM and was accompanied by downregulation of Akt and the active form of MDM2, indicating a possible mechanism. GA also produced a p53/ATM-independent increase in the levels of p21-a potent inducer of cell-cycle arrest."

So contrary to what some on here have indicated K does not reactivate mutant p53, but actually promotes its destruction allowing it to be replaced with the functional wild type protein (which is generally ihibited by the very presence of the mutant p53).

Another interesting note is that Hsp90 has been linked to Alzheimer's disease (per the below) and down regulation has been linked to inhibiting the formation of tau (the protein responsible for Alzheimer's) so there is that implication if K can cross the blood brain barrier

"Consistent with previous research on Hsp90 clients in cancer, we provide evidence that a loss of HDAC6 activity augments the efficacy of an Hsp90 inhibitor and drives client degradation, in this case tau."

In summary, it appears that indeed the key to K's efficacy is Hsp90 inhibition via HDAC6 and HDAC2 inhibition. This is an insight that personally I did not have despite having read those posters numerous times. Thank you Orion for helping me attain this clarity.