RNR inhibitor BBI-825

An orally available small molecule selective inhibitor of ribonucleotide reductase (RNR), with potential antineoplastic activity. Upon oral administration, RNR inhibitor BBI-825 targets, binds to and inhibits the activity of RNR, which decreases the pool of deoxyribonucleotide triphosphates (dNTPs) available for DNA synthesis. This disrupts DNA synthesis and extrachromosomal DNA (ecDNA) assembly and repair, resulting in cell cycle arrest and tumor growth inhibition. RNR, an enzyme that catalyzes the conversion of ribonucleoside diphosphate to deoxyribonucleoside diphosphate, is essential for de novo DNA synthesis and plays an important role in cell growth; it is overexpressed in many cancer cell types and is associated with increased drug resistance, cancer cell growth and metastasis.