Yet more - potential blockbuster stuff, as it may relate to the...

Yet more - potential blockbuster stuff, as it may relate to the Kazia drug, paxalisib.

You would be sick of reading this research everyday -  but its all massive, very recent (always within the last few weeks)..... potential life affecting information, for large populations.

Am just in the mood for posting at present - not that all this extraordinary information makes the slightest difference to the share price.

So to always be very selective and only present high quality, western university research here......whereby paxalisib is specifically mentioned - or very clearly, this brain penetrant, multi-isoform, safe PI3K/AKT / mTOR drug  is very apparently, relevant to the research.

Again here - Paxalisib right now, looks to be the go to drug......in a market that would make pax a household name worldwide. So trying to keep this as short and simple, as possible :

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Remember the recent Huntsman University UTAH research. And specific discussion on what paxalisib offered, as a newer generation, mTOR inhibitor. In short, according to Huntsman - finally paxalisib is a breakthrough drug therapy that works in this mTOR area. (We knew that already, but it is most eloquently explained here ) See below , from the abstract.

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So to the main topic of this post at very bottom - 4 th May from Department of Medicine, University of Wisconsin -  detailed research on the need for more advanced mTOR drugs to treat ageing of the human body.

Cynical - than read for yourself, at the very bottom.  Even to my surprise - a previous FDA Clinical Trial with Everolimus (a drug mentioned by Kazia in presentations, as possible competition)

The largest clinical trials to date have investigated whether mTOR inhibition can improve the function of the aging immune system. The first clinical trial was done with 218 adults aged ≥65 years without unstable medical conditions to determine whether the rapalog everolimus improved the function of the aging immune system as assessed by response to influenza vaccination⁸²

and a QUOTE from below info

"We conclude by discussing what work remains to be done and the questions that will need to be addressed to make mTOR inhibitors part of the standard of care for diseases of aging."



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POSTER PRESENTATIONS - PROFFERED ABSTRACTS| APRIL 04 2023 HUNTSMAN
Abstract 427: Newer generation mTOR inhibition represents effective therapeutic strategy for BRAF-mutant melanoma
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..."phase II clinical trials of mTOR inhibitors have not shown clinical advantage. This may be due to multiple reasons: firstly, mTOR inhibitors, such as rapamycin, function by destabilization of the mTORC1-Raptor complex while leaving the mTORC2-Rictor complex, intact. Rictor enables mTORC2 to directly phosphorylate Ser473, and facilitates Thr308 phosphorylation by PDK1. As both AKT and SGK are phosphorylated by mTORC2 and PDK1 to facilitate downstream signaling through mTORC1, residual activity of mTOR incompletely suppressed by rapamycin may still be sufficient to drive melanoma progression. Thus, we evaluated second and third generation mTORC inhibitors, including a dual PI3K/mTOR inhibitor, that target both mTORC1 and 2 complexes and lead to sustained suppression of PI3K>AKT signaling. The dual PI3K/mTORC inhibitor Paxalisib.."

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• Published: 04 May 2023

Targeting the biology of aging with mTOR inhibitors

• Joan B. Mannick &
• Dudley W. Lamming

Nature Aging (2023)Cite this article

Abstract

Inhibition of the protein kinase mechanistic target of rapamycin (mTOR) with the Food and Drug Administration (FDA)-approved therapeutic rapamycin promotes health and longevity in diverse model organisms. More recently, specific inhibition of mTORC1 to treat aging-related conditions has become the goal of basic and translational scientists, clinicians and biotechnology companies. Here, we review the effects of rapamycin on the longevity and survival of both wild-type mice and mouse models of human diseases. We discuss recent clinical trials that have explored whether existing mTOR inhibitors can safely prevent, delay or treat multiple diseases of aging. Finally, we discuss how new molecules may provide routes to the safer and more selective inhibition of mTOR complex 1 (mTORC1) in the decade ahead. We conclude by discussing what work remains to be done and the questions that will need to be addressed to make mTOR inhibitors part of the standard of care for diseases of aging.