Search results for "MTH1"

The hMTH1 paradox: antioxidants recommended in cancer?

2014

Summary Activated Ras GTPase signalling is a critical driver of oncogenic transformation and malignant disease. Cellular models of RAS-dependent cancers have been used to identify experimental small-molecules, such as SCH51344, but their molecular mechanism of action remains generally enigmatic. Here, using a chemical proteomic approach we identify the target of SCH51344 as the human mutT homologue MTH1, a nucleotide pool sanitising enzyme. Loss-of-function of MTH1 impaired growth of KRAS tumour cells whereas MTH1 overexpression mitigated sensitivity toward SCH51344. Searching for more drug-like inhibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 acti…