Ketohexokinase Inhibitor

An orally bioavailable pyrimidinopyrimidine compound that acts as a potent, reversible and ATP-competitive inhibitor of human hepatic KHK activity (KHK-C isoform; IC₅₀ = 12 nM in a transcreener ADP assay) and efficiently blocks fructose-1-phosphate secretion (IC₅₀ ≤ 400 nM in HepG2 cells). Displays ~50-fold lower potency towards metabolic kinases, namely, ribokinase, hexokinase and adenosine kinase, and minimal binding affinities to diverse receptors and ion-channels, and excellent selectivity among a panel of 31-kinases including Akt1, AMPK, CaMKI/II, InsR, IRAK4, PKA and PKCθ (IC₅₀ >>10 µM). Shown to minimally affect the activities of human cytochrome p450 isozymes (1A2, 2C19, 2D6, 2C9 and 3A4), and exhibit high volume of distribution and high rate of clearance in rats.

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Maryanoff, B.E., et al. 2011. ACS Med. Chem. Lett.2, 538.

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

Toxicity: Standard Handling (A)