Monday, January 08, 2018 4:20:59 PM
From the COTI-2 paper:
"However, there were other cell lines such as HCT-115, H292, and H460 with wild type P53 that were also highly sensitive to COTI-2 treatment. This suggests that COTI-2 may affect mutant P53 in human tumors, but likely has additional effects on other targets in the PI3K/AKT/mTOR pathway."
Don't know if they looked at the effects of activation on wild-type p53, but it apparently does more than just re-activate mutant p53.
Re: PRIMA-1 byproducts and metabolites, I believe they are using methylated PRIMA-1, which may have different byproducts. Haven't heard about AEs in APR-246. There are always good possibilities that new drugs have some toxicity.
APR-246 AML paper also shows it works in p53 mutant and p53 wild-type cells:
"Also, the fact that APR-246 is effective in both mutated and non-mutated AML cells might be explained p53-independent mechanisms of action."
Some more on APR-246 p53 mutant dependent and independent MOAs:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742820/
"Its main cellular mechanism of action is the induction of apoptosis, mediated by the caspase activation. PRIMA-1 as well as APR-246 triggers an upregulation of genes involved in cell cycle control and apoptosis in mutant-p53 and wild-type p53 cancer cells. Anyway, 15 years after their discovery, it clearly appears that PRIMA-1/APR-246 have also p53-independent effects, as oxidative and ER stress, which emphasize their efficacies and extend their possible clinical uses, on tumor cells, independently of the p53 status."
Molecular biology of cancer is very complicated. Hoping that these p53 drugs play out well, especially kevetrin.
Recent IPIX News
- Form 8-K - Current report • Edgar (US Regulatory) • 02/01/2024 01:30:25 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 12/05/2023 09:25:58 PM
- Form 10-Q - Quarterly report [Sections 13 or 15(d)] • Edgar (US Regulatory) • 11/20/2023 09:05:44 PM
- Form NT 10-Q - Notification of inability to timely file Form 10-Q or 10-QSB • Edgar (US Regulatory) • 11/15/2023 01:00:19 PM
- Form 8-K - Current report • Edgar (US Regulatory) • 10/30/2023 08:15:25 PM
- Form 10-K - Annual report [Section 13 and 15(d), not S-K Item 405] • Edgar (US Regulatory) • 09/28/2023 01:00:08 PM
Kona Gold Beverages, Inc. Announces Strategic Initiatives and Corporate Direction Changes • KGKG • Aug 2, 2024 2:00 PM
POET and Luxshare Tech Expand Product Offerings for Artificial Intelligence Networks • POET • Aug 1, 2024 9:28 AM
Management Discusses Financial Filings of Global Arena Holding Inc., for 10-K 2023 and 10-Q, 1st Quarter 2024 • GAHC • Aug 1, 2024 9:14 AM
VAYK Announces LOI to Acquire $1 Million Home Service Company to Support Airbnb Business • VAYK • Aug 1, 2024 9:00 AM
Duane Forrester Joins INDEXR as SVP of Search • MONI • Jul 31, 2024 11:46 AM
Lingerie Fighting Championships Help Fulfill Death-Bed Promise With First Major Motion Picture • BOTY • Jul 31, 2024 9:00 AM