Buckeyes,

BD2-selective BET inhibitor = good
Pan-BET inhibitor = bad

The latest study confirmed the outstanding safety (and efficacy) of BD2-selective drugs, like apabetalone and RVX-2197.  Extremely convincing and encouraging new data, imo.

BD2-selective inhibition is clearly superior to pan-BET inhibitors that inhibit far too much of everything and are also too toxic for long-term use in chronic diseases, where they cause bigger problems for the body than the ones they solve.   

But what I also noticed in the publication was that (in cells) at higher doses of apabetalone (Apa20, 20 uM), apabetalone behaved in a less BD2-selective way = bad.  The publication indicated that doses of apabetalone above 15 uM caused the effects of apabetalone to resemble more or less like that of a pan-BET inhibitor = bad (at this high dosage).   

apabetalone at doses above 15 uM = lower BD2-selectivety, and lower beneficial effects and safety.

So I thought to myself, "Wait, what dosage level did we use in BETonMACE and was it maybe a too-high of a dose where the benefits of BD2-selectivity were lost or dimished?"  

Once I was able to make conversion estimates from uM's to mg's I was able to estimated that the dosage used in BETonMACE was nowhere near levels that would lower BD2-selectivity and its beneficial effects.  In BETonMACE plasma apabetalone was registering only a small fraction (1 uM vs 15 uM) of the uM dosage that would be considered deliterious to BD2-selectivity and it's beneficial effects.

I hope this helps!

JMHO