Hello,

According to Gad et al., (Nature. 2014;508(7495):222-7), «MTH1 is non-essential in normal cells», however, «cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death». In results, MTH1 protein is good target for killing of cancer cells. My answer is very simple: it is necessary to find or synthesize MTH1 inhibitors, that have minimal side-effects. For example, (S)-crizotinib was proposed as an attractive inhibitor of MTH1 protein (Huber et al., 2014).

Good luck!

Hi, as far as our research findings tell us, it would look like indeed the side effects are minimal. We have massive research ongoing regarding the inhibitors published in the Nature paper. If you would like to try the MTH1 inhibitors in the context of your own experiments, please contact the corresponding author.

Good luck! 

Thank you Dr Jordi Carreras Puigvert.

My concern is about the stress condition of actively dividing cells e.g. bone marrow cells, gut lining etc. where cells are dividing at more faster rate than the other cells.

So is there any signs of importance of MTH1 protein in those cells, in protecting the DNA. Because if its protecting those cells from the oxidation stress generated due to high cell activity (cell division), its inhibition is going to result in bone marrow suppression. 

Can you confirm the above statement ?

Hi Mahender,

I am not actively involved in the experiments regarding MTH1 inhibition, but I think that in the papers published so far you will find the answers to your questions.

Cheers,

Jordi