> “This is an exciting paper for two reasons,” says David Pellman, associate director for basic science at Dana-Farber/Harvard Cancer Center, who was not involved in the study. “First, Yaffe and colleagues make an important advance for the rational design of drug therapy combinations. Second, if you like scientific mysteries, this is a riveting example of molecular sleuthing. A drug that was thought to act in one way is unmasked to work through an entirely different mechanism.”
Since my startup compiles all genomic knowledge from the published literature, of course the first thing I did was search the literature. The first article that comes up with a quick search for MTH1 and TH588 was from 2014 [0], which basically says TH588 is a first-class MTH1-inhibitor effective in treating certain cancer cells. Then in 2016, another article says that's not its primary mechanism of effectiveness [1]:
> In particular, we identified tubulin as the primary target of TH287 and TH588 responsible for the antitumor effects despite the nanomolar MTH1-inhibitory activity in vitro.
Tubulin of course is part of the mitotic spindle which the posted article claims was discovered as the actual target upon which TH588 acts.
I've found around 10 other papers between 2016 and 2018 that further conclude that TH588 doesn't act primarily as an MTH1-inhibitor.
[0] https://www.ncbi.nlm.nih.gov/pubmed/24695224 [1] https://www.ncbi.nlm.nih.gov/pubmed/27210421