Thionicotinamide

Chemical Properties

yellow powder

Uses

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].

Definition

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

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].

References

[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