Guanine synthesis inhibitor for glioblastoma

A small molecule prodrug inhibitor of the guanine synthesis enzyme IMPDH2, which is converted to its active form by NAD salvage enzymes, could help treat glioblastoma by causing nucleotide imbalance, interfering with DNA synthesis required for proliferation, without affecting other dividing cells.

In pooled primary mouse glioblastoma cells from tumors that spontaneously arose in mice deficient in three common glioblastoma tumor suppressors, a screen for compounds that inhibited glioblastoma proliferation with IC50s in the nanomolar range, combined with a screen to rule out antimitotic compounds, identified (N-(pyridin-3-yl)thiophene-2-carboxamide, dubbed gliocidin, which inhibited tumor cell proliferation with an IC50 of 200nM, but had no observable effect on healthy dividing mouse fibroblasts...