Biotech Values

[genisi]

I believe PSI-938' different resistance profile was indeed one of the reasons it was advanced in the clinic along with it's different prodrug cleavage pathway and phosphorylation pathway but it was not designed (in part) to provide resistance against the 282T mutant, that was a lucky coincidence which was not expected. I was certain I've read about this a while ago and just managed to find that paper:

It was previously suggested that resistance due to the S282T mutation was directed toward the ribose moiety: incorporation of the 2'-C-methyl-modified nucleotide in the primer position could result in steric hindrance between the methyl group and the ribose of the incoming nucleoside triphosphate (43). Our data showing that PSI-352938 retained its activity against the S282T replicon were therefore quite surprising.

http://aac.asm.org/content/55/6/2566.full