Replies to post #70963 on Innovation Pharmaceuticals Inc (IPIX)

[Astavakra]

Could you please clarify what David Lane said? Having a hard time making sense of what you wrote. TIA

[KMBJN]

Kevetrin seemed to stabilize CA-125 (ovarian cancer biomarker) in the lady with ovarian cancer who received 7 cycles / low doses of K.

Speaking of APR-246 and ovarian cancer, I see Aprea started a Phase I/II study in ovarian cancer in combination (just for you George) with platinum based chemo:

http://aprea.com/2014/dosing-initiated-in-phase-iii-clinical-trial-of-apr-246-in-ovarian-cancer/

Their first Phase I/II study was as monotherapy, against advanced blood and prostate cancer.

I guess their preclinical work showed it can re-sensitized ovarian cancer cells after they become refractory to platinum based chemo, so they decided a combo trial in ovarian cancer.

[sox040713]

Based on what I understand, Kevetrin degrades but does not restore mutant p53. From their website:

"Oncogenic mutant p53 is often highly expressed and is hyperstable and drives tumor formation, invasion and metastasis. Mutant p53 cancers are dependent on their hyperstable mutant p53 protein for survival. Thus targeting mutant p53 for degradation is an excellent strategy to manage tumors that are addicted to mutant p53 for survival. The underlying mechanism of mutant p53 stabilization is the formation of a stable complex between HSP90, which is highly and ubiquitously upregulated in cancer cells, and mutant p53, which inhibits E3 ligase MDM2. Kevetrin strongly destabilizes mutant p53 at the level of protein degradation. Kevetrin downregulates the HDAC6, an essential positive regulator of HSP90. Downregulation of HDAC6 releases mutant p53 from the stabilized complex and enables E3 ligase mediated degradation. Kevetrin preferentially degrades mutant p53 rather than wild type p53. Kevetrin by virtue of depleting mutant p53 may be able to dramatically chemosensitize mutant p53 cells to chemotherapeutic drugs."

Kevetrin I hope does the same - gets the mutated p53 to fold into a proper form that then restores some of its lost function.