Mer is a member of the TAM (Tyro3, Axl and Mer) receptor tyrosine kinase (RTK) subfamily with growth-arrest-specific-6 (Gas6) as one of the endogenous ligands. Elevated Mer activation has been strongly associated with the oncogenesis of a number of human cancers. Recently, Mer has also been shown to play important roles in regulating macrophage activity and platelet aggregation[2]. UNC2881 is a specific Mer tyrosine kinase inhibitor with an IC50 of 4.3 nM, and its selectivity is 83-fold and 58-fold higher than that of Axl and Tyro3, respectively[2]. When applied to live cells, UNC2881 inhibits steady-state Mer kinase phosphorylation with an IC50 value of 22 nM. Treatment with UNC2881 is also sufficient to block EGF (epidermal growth factor)-mediated stimulation of a chimeric receptor containing the intracellular domain of Mer fused to the extracellular domain of EGFR. In addition, UNC2881 potently inhibits collagen-induced platelet aggregation, suggesting that this class of inhibitors may have utility for prevention and/or treatment of pathologic thrombosis[2]. In mice, UNC2881 had high systemic clearance (94.5 mL/min/kg) and 14% oral bioavailability. The terminal half-life was 0.80 h. The volume of distribution was 2-fold greater than the normal volume of total body water (0.70 L/kg)[2].
UNC2881 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human platelets
3 µM
1 hour
Inhibition of collagen-induced platelet aggregation
Inhibition of Mer kinase phosphorylation in human 697 B-ALL cells after 1 hr by Western blot analysis, IC50=0.022 μM
24219778
mouse 32D-EMC cells
Function assay
Inhibition of EGF-induced human intracellular domain of Mer/extracellular domain of EGFR phosphorylation expressed in mouse 32D-EMC cells after 1 hr by Western blot analysis
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