TMT on an Astral - quan isn't as good but coverage is high enough to reveal new off-target effects!

 

I guess this paper isn't new, I just saw it on Linkedin posted by this guy 

and I'd totally missed it.

If you're here for the mass spectrometry comparisons, they summarized them far more succinctly than I could. I have a tendency to type too much. 

No real surprise there, MS2 TMT isn't quite as good at quan, particularly if you're doing lazy math and just considering fold change ratios rather than real significance cutoffs 😇, but the higher speed of the Asstral gets you a lot more coverage. 

However, the reason this paper is here is because I have personally looked for off-target effects in cells treated with a similar compound...and I haven't found confident hits. We did a relatively deep dive into on that isn't studient in this paper (MRTX1133...unless they changed the name...they do that with these drugs all the time...) and it's chemistry is definitely different, but multiple organic chemists I know predicted it would also have off-target cysteine binding. I have zero hits. 

Again, not the same drugs, but these compounds are very very very selectively engineered. There are like 40 companies competing with 200+ compounds and there have been limited off-target reports on the ones that are getting tentative blessings by the FDA and other regulatory bodies. This should make you think - if these are happening these things are low low low abundance and rare, but here we are. With a pile of high resolution data with possibly mediocre quan on the Astral that show a solid number of off-target effects. That's worth thinking about.