Ann: Breakthrough Zantrene Heart Protection Discovery, page-292

You aren't really giving me much to work with, @bourse.

I am applying the same level of scepticism towards that reddit poster as you are to the scientific developments of RAC and Daniel. Until they or you provide proof of their academic position, I will remain sceptical. I, however, am prepared to put my reputation on the line. I completed a degree in Nutrition (2018), a Masters of Dietetics (2020), and had a published paper in Alzheimer's disease research while I was still a student (one of very few in my class to do so; 1). My full name is first on the paper.

1 https://www.researchgate.net/publication/344614977_Dietary_saturated_fats_and_apolipoprotein_B48_levels_are_similarly_associated_with_cognitive_decline_in_healthy_older_aged_Australians

What results have been published in the interim that should assuage his specific concerns?

The poster in question is beating a very old anthracycline drum. They have not gone through the historic literature to the level required to understand it from an FTO point of view. I know this because I have had another lengthy discussion with a PhD graduate and CEO of a biotech company in the USA. He looked at 2 Zantrene papers and decided that it was not a good investment. The guy didn't even know about the historical preclinical papers that clearly show the atrocious anthracycline efficacy of Zantrene compared to approved and discarded anthracyclines.

To put things very simply, Zantrene was always used in an anthracycline way, which we now know is completely the wrong way of doing it. Despite the missuse of Zantrene clinically, it was still able to demonstrate efficacy in certain patients when used in a way that would most resemble an FTO regimen. The dosing regimens that demonstrated any efficacy at all were consistent over 5-7 days and ranged from doses of 60 - 250 mg/m2 per day. A dosing regimen aimed at targeting FTO is going to have to be done consistently over longer periods of time. The poster doesn't address this, rather jumps up and down about lack of efficacy and clinical maturity being a joke. The major take away from the clinical maturity is that even at doses that far exceeded those required for FTO inhibition, patients were able to tolerate the drug, there was extensive cardiac safety (even when paired with a cardiotoxic agent), and that there was some efficacy.

The 'results' or data that you should consider is the following:

- Zantrene identified as the most potent FTO inhibitor out of 260,000 different compounds
- Preclinical studies identify Zantrene as the least potent anthracycline. Even below a drug that was never approved it was so bad (Zantrene achieved approval)
- 28 different cancer types linked to FTO overexpression (almost 100 papers over the last ~5-6 years)
- 13 different anti-cancer therapies shown to synergise with either Zantrene, an FTO inhibitor, or an FTO knockdown model
- Zantrene highly effective at low nM concentrations in melanoma, AML, breast, glioblastoma, and pancreatic cancers
- Zantrene shown to synergise with anthracyclines as well as provide cardioprotection
- Zantrene shown to synergise with HMAs, BCL-2 inhibitors, and nucleoside analogues
- Clinical data demonstrating significantly reduced cardiac damage in hundreds of patients
- Clinical data demonstrating efficacy in low and high-dose consistent regimens
- Clinical data demonstrating 100% efficacy in patients selected by sensitivity screening assays

I have generated countless posts on HotCopper addressing each of these data points. Using the advanced search function should provide you with enough opportunity to see my interpretation of the data at hand.