An enhanced in solution stable gallocyanine analog that directly and reversibly targets human LRP5/6 (low density lipoprotein-related protein 5/6), and disrupts its interaction with Dkk (Dickkopf) in a competitive manner. Shown to potently reverse DKK1/2/4-mediated inhibition of WNT3A-stimulated reporter gene activity (IC50 ~ 10 - 30 µM in in NIH 3T3 cells) with no effects on sFRP4-mediated inhibition of Wnt signaling. Blocks Dkk-2 - alkaline phosphatase binding to cells expressing LRP5 (IC50 = 1 µM in LRP5 transfected NIH 3T3 cells). Reduces blood glucose levels, improves glucose tolerance, and increases insulin sensitivity in type 2 diabetic mice (1.5 mg/kg, i.p. daily), mainly via its antagonistic action on DKK2. These effects are not observed in DKK2 -/- mice.
Synonyms: Dkk Inhibitor II, IIIC3a - Calbiochem; 9-Carboxy-3-(dimethyliminio)-6,7-dihydroxy-10-methyl-3H-phenoxazin-10-ium iodide
Molecular Formula: C16H16I2N2O5
Molecular Weight: 570.12
Linear Structural Formula: C16H16I2N2O5
Purity: >=90% (HPLC)
Biochem Physiol Actions: Reversible: yes
Legal Information: CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes: Li, X., et al. 2012. Proc. Natl. Acad. Sci. USA109, 11402.