Merck, 5054790001, SIRT1/2/3 pan Inhibitor

General description
A thienopyrimidinylcarboxamide that acts as a highly potent, reversible pan sirtuin (SIRT) inhibitor (IC₅₀ = 15, 10, and 33 nM for SIRT1, 2, and 3, respectively). Shown to bind to the SIRT catalytic site and occupy both the nicotinamide C-pocket and acetyl lysine substrate channel. Exhibits high selectivity over a panel of protein kinases, nuclelar receptors, GPCRs, and ion-channels (IC₅₀ >10 µM). Poorly affects hERG and cytochrome P450s (>50 µM). Exhibits desirable stability in microsomal preparations (human CLint = 15.8 µL/min/mg, mouse CLint = 12.7 µL/min/mg) and high solubility (297 µM), and low LogD (2.73).
Biochem/physiol Actions
Primary Target
SIRT1/2/3
Reversible: yes
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
Disch, J.S., et al. 2013. J. Med. Chem.57, 1275.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)