Thionicotinamide

yellow powder

Thionicotinamide (TN) is an NADK inhibitor prodrug and lead compound[2]. As a lead compound, thionicotinamide sensitizes CEM-CCRF, MOLT-4, RL, and C85 cell lines to chemotherapeutic agents and reduces cellular NADP/NADPH pools[2][3].

Thionicotinamide is the active moiety of two previously identified NADK inhibitors, NADS and NADPS. Treatment of C85 cancer cells with thionicotinamide resulted in an identical loss of dihydrofolate reductase levels, a G1/S block, and similar toxicity profiles as NADS and NADPS; that is, thionicotinamide is a prodrug and is converted intracellularly to NADPS[1].

In vivo administration of thionicotinamide at 100 mg/kg every other day significantly reduces tumor growth in C85 xenografts (four cycles) and RL diffuse large B-cell lymphoma xenografts (five cycles) without observed neurotoxicity or weight loss[3].

[1] Philip M Tedeschi. “Suppression of Cytosolic NADPH Pool by Thionicotinamide Increases Oxidative Stress and Synergizes with Chemotherapy.” Molecular Pharmacology 88 4 (2015): 720–7.
[2] Tedeschi, P. M., Bansal, N., Kerrigan, J. E., Abali, E. E., Scotto, K. W., & Bertino, J. R. (2016). NAD+ Kinase as a Therapeutic Target in Cancer. Clinical Cancer Research, 22(21), 5189–5195. https://doi.org/10.1158/1078-0432.ccr-16-1129
[3] Tedeschi, P. M., Lin, H., Gounder, M., Kerrigan, J. E., Abali, E. E., Scotto, K., & Bertino, J. R. (2015). Suppression of Cytosolic NADPH Pool by Thionicotinamide Increases Oxidative Stress and Synergizes with Chemotherapy. Molecular Pharmacology, 88(4), 720–727. https://doi.org/10.1124/mol.114.096727