606015

Thymidylate Kinase Inhibitor, YMU1

The Thymidylate Kinase Inhibitor, YMU1 controls the biological activity of Thymidylate Kinase. This small molecule/inhibitor is primarily used for Phosphorylation & Dephosphorylation applications.

• Synonym(s): Thymidylate Kinase Inhibitor, YMU1, Ethyl 4-(2-(4,6-dimethyl-3-oxoisothiazolo[5,4-b]pyridin-2(3H)-yl)acetyl)piperazine-1-carboxylate, TMPK Inhibitor
• Empirical Formula (Hill Notation): C₁₇H₂₂N₄O₄S
• CAS Number: 902589-96-2
• Molecular Weight: 378.45
• MDL number: MFCD27952931
• UNSPSC Code: 12352200

Properties

• Quality Level: 100
• assay: ≥99% (HPLC)
• form: solid
• potency: 610 nM IC₅₀
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: white
• solubility: DMSO: 3.3 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: CC1=NC(SN(CC(N2CCN(CC2)C(OCC)=O)=O)C3=O)=C3C(C)=C1

Description

General description

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.).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
TMPK

Reversible: yes

Target K_i: 180 nM for TMPK

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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.

Other Notes

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

Legal Information

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

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable