An orally bioavailable pyrimidinopyrimidine compound that acts as a potent, reversible and ATP-competitive inhibitor of human hepatic KHK activity (KHK-C isoform, IC50 = 12nM in a transcreener ADP assay) and efficiently blocks fructose-1-phosphate secretion (IC50 400nM 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 PKCtheta (IC50 >> 10uM). 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. Molecular Formula: C21H26N8S2HCl Solubility: DMSO Molar Mass: 495.5 Storage and Stability: Lyophilized powder may be stored at -20C. Stable for 12 months at -20C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
Molecular Weight:
495.5
Purity:
97% (HPLC)
Form:
Supplied as a yellow solid.
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