UNC2250

UNC2250 is a phosphorylation of endogenous Mer inhibitor with an IC50 of 9.8 nM and blocked ligand-stimulated activation of a chimeric EGFR-Mer protein.IC50 Value: 9.8 nM [1]Target: Othersin vitro: UNC2250 is 160-fold more active for Mer versus Axl and 60-fold versus Tyro3. UNC2250 had a moderate half-life, clearance, and volume of distribution as well as reasonable oral bioavailability and good solubility and was thus chosen for characterization of kinase selectivity and further evaluation in cell-based studies of Mer activity. UNC2250 efficiently inhibited ligand-dependent phosphorylation of a chimeric protein consisting of the extracellular and transmembrane domains of the epidermal growth factor (EGF) receptor and the intracellular tyrosine kinase domain of Mer. Moreover, UNC2250 incubation inhibited colony formation in soft agar cultures of the BT-12 rhabdoid tumor and the Colo699 NSCLC cell lines. In the Colo699 NSCLC cell line, the concentrations of UNC2250 required to inhibit colony formation and Mer phosphorylation were similar. These data suggest that the functional antiproliferative activity mediated by UNC2250 resulted from Mer inhibition rather than a consequence of off-target inhibition of other kinases [1,2].In vivo:

Signaling Pathways >> Protein Tyrosine Kinase/RTK >> TAM Receptor

Research Areas >> Cancer

[1]. Zhang, W., et al., Pseudo-cyclization through intramolecular hydrogen bond enables discovery of pyridine substituted pyrimidines as new Mer kinase inhibitors. J Med Chem, 2013. 56(23): p. 9683-92.

[2]. http://www.google.com/patents/WO2013177168A1

Bemcentinib (R428) | Gilteritinib | BMS-777607 | TP-0903 | LDC1267 | CEP-40783 | SGI-7079 | 2-D08 | Glesatinib hydrochloride | Ningetinib | NPS-1034 | UNC 2881 | R916562