6-Aminonicotinamide

6-Aminonicotinamide, a potent antimetabolite of nicotinamide, is competitive NADP⁺-dependent enzyme glucose-6-phosphate dehydrogenase (G6PD) inhibitor (K_i=0.46 μM). 6-Aminonicotinamide resultis ATP depletion and synergizes with DNA-crosslinking chemotherapy agents, such as Cisplatin, in killing cancer cells^[1][2][3][4]. In Vitro:6-Aminonicotinamide (100 nM; 7 days) causes a significant decrease in the human AR+, hormone-sensitive prostate cancer cell lines LNCaP and LAPC4, as well as the CRPC-derivative C4-2 and 22Rv1 cell models. 6-Aminonicotinamide (100 nM ± 10 nM R1881 as indicated for 3 days) increases both basal- and R1881-mediated ROS levels, suggesting 6-Aminonicotinamide is blocking the cells' antioxidant defense. 6-Aminonicotinamide also increases ROS levels in C4-2 cells^[3]. In Vivo:6-Aminonicotinamide (20 mg/kg; i.p.; thress times; days 1, 10 or 11, and 21) alone induces a small but significant tumor growth delay (4.3+/-0.8 days). Treatment with 6-Aminonicotinamide followed by radiation induces a tumor growth delay of 57.0+/-3.8 days in CD8F1 breast tumor model^[4].