A cell-permeable, non-toxic pyridineisothiazolone compound that acts as a potent, reversible, and ATP-competitive inhibitor of human Thymidylate kinase (TMPK) (IC₅₀ = 610 nM; K_i = 180 nM). Does not affect the activity of Thymidine kinase 1 (TK1) (IC₅₀ >10 µM). Its action appears to involve blocking the interaction of Mg²⁺ with Asp¹⁵ in the catalytic domain. Shown to specifically reduce dTTP (deoxythymidine triphosphate) by 30 to 40% in HCT-116 p53^-/- cells, without affecting dATP, dCTP, and dGTP levels. Significantly increases (3 to 35 fold) the sensitivity of a variety of tumor cell lines to doxorubicin (>Cat. No. 324380), and shrinks tumor size in HCT-116 p53^-/- xenografted mouse model (doxorubicin, 1.25 mg/kg twice a week, i.p.; YMU1, 5 mg/kg thrice a week, i.p.).

Cell permeable: yes

Primary Target
TMPK

Reversible: yes

Target K_i: 180 nM for TMPK

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C. Use only fresh DMSO for reconstitution.

Hu, C.M., et al. 2012. Cancer Cell22, 36.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany