Our Science
Genase Therapeutics develops a potent and selective orally bioavailable small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), a critical enzyme in the de novo pyrimidine biosynthesis. Multiple independent genetic and phenotypic screens in cancers addicted to cell growth-inducing oncogenes identified DHODH as a target that can be therapeutically exploited*.
This metabolic vulnerability has been demonstrated in both solid and hematological malignancies driven by oncogenes such as MYC, KRAS and BRAF. Building on the initial discovery of novel DHODH inhibitors by prof. Sonia Lain and colleagues of the Karolinska Institute, Genase Therapeutics develops its candidate drug GTX-196 as a monotherapy in aggressive hematological maligancies, as well as a combination therapy in solid tumors for colorectal cancer, where patients are stratified by certain biomarkers.
Tumors heavily rely on do novo pyrimidine synthesis
Tumor cells heavily rely on the energy-demanding de novo pyrimidine biosynthesis to replenish their nucleotides, while for healthy normal cells the energy-conserving pyrimidine salvage pathway (recycling of nucleotide intermediates) is sufficient when the de novo pyrimidine biosynthesis is blocked.
Oncogene addicted tumors rely on de novo pyrimidine synthesis: Key role for DHODH
Oncogenes such like MYC, RAS and BRAF provide powerful mitogenic signals that create a dependency on DHODH to sustain cancer cell growth.