I would argue that they are far from done with preclinical work. From what I can see, their research was focused primarily on developing and then improving an FTO inhibitor, and then determining if 18097 could inhibit FTO in some basic cellular and in vivo models. While it is great that the study has yielded some efficacy data, my understanding is there would need to be much more work done to gather in-depth efficacy data as well as toxicity, pharmacokinetic, and safety data before progessing into phase 0 (human microdose) or phase 1 clinical trials (below; 1). This would all be needed before they could even be remotely 'close' to RAC and Zantrene. As we know, RAC have a mountain of efficacy and safety data in breast cancer patients, at doses that far exceed theorised regimens required for FTO inhibition. RAC can enter into phase II clinical trials for breast cancer straight off the bat, which I think could put the lead time at around a minimum of 36 months. I don't think this paper whittles our lead at all.
1 https://www.profil.com/knowledge-center/trial-stagesYes, the IC50 for 18097 is 640 nM, but this is far from specific in my opinion. For example, brequinar has an IC50 of 712 nM for FTO, which is below the 1uM cut off. Great, but it also has an IC50 of 19-20nM for DHODH. What this means is when brequinar makes its way into an organism, it will bind with much high specificity to DHODH, which makes targeting FTO challenging. There is nothing to suggest that this can't also happen to compound 18097.
RAC is way ahead in all cancer indications where clinical responses have been determined, not just AML.
Personally, I would be looking at Dac51 to make estimations on lead time. While it does seem to have some weak anti-cancer properties in some in vivo models, it is the next most potent compound and clinically advanced. I think it would be interesting to estimate the lead time in months or years, but I am not sure of the best way to do this. IC50 value of 18097, the most potent FTO inhibitor, was
179 μmol/L for ALKBH5 (Fig. S2G), which is about280-fold greater than that to FTO."
