benzamide riboside

**Benzamide riboside (BR)** is a synthetic C-nucleoside and a novel anticancer agent exhibiting potent cytotoxic activity against a variety of malignant human tumor cell lines. Its antitumor effect is primarily mediated by inhibition of inosine 5′-monophosphate dehydrogenase (IMPDH), a key enzyme in de novo guanylate biosynthesis, which catalyzes the formation of xanthine 5′-monophosphate from inosine 5′-monophosphate using NAD as a cofactor[1][5][7]. After intracellular phosphorylation, BR is metabolized predominantly to benzamide adenine dinucleotide (BAD) via NMN adenylyltransferase; BAD acts as a potent inhibitor of IMPDH[1][5]. BR's mechanism also includes induction of apoptosis via mitochondrial cell death pathways with release of cytochrome c, activation of caspases 3 and 9, and PARP cleavage[4][7]. At higher concentrations, BR can cause necrosis due to ATP depletion[3]. BR has a second mechanism involving downregulation of dihydrofolate reductase (DHFR). This is mediated by BAD’s inhibition of NAD kinase, which lowers cellular NADP/NADPH levels and destabilizes DHFR[9]. Preclinical studies showed oncolytic effects against leukemia, ovarian carcinoma, and other cancer cell models[2][3][4][7].

Other names

3-β-D-ribofuranosyl benzamideBR