Potent and highly selective Mer receptor tyrosine kinase (MerTK) inhibitor in vitro and in vivo.
UNC2250 is a potent and highly selective Mer receptor tyrosine kinase inhibitor (MerTK IC50 = 1.7 nM; Tyro3/Axl IC50 = 100/270 nM) that reduces endogenous Mer phosphorylation level (697 B-ALL IC50 = 9.8 nM post 1h treatment) and blocks ligand-stimulated activation of a chimeric EGFR-Mer in cells. UNC2250 inhibits colony-forming potential in rhabdoid (by 36% at 100 nM; BT-12 cells) and NSCLC tumor cells (Colo699 IC50 = 100 nM) with good pharmacokinetic properties. UNC2250 is reported to reduce mortality in a murine LPS-induced acute lung injury (ALI) model (2 mg/kg i.v. )
The NLR family pyrin domain-containing 3 (NLRP3) multiprotein complex is associated with neuroinflammation and poor prognosis after subarachnoid hemorrhage (SAH). Accumulating evidence shows that Mer tyrosine kinase (MerTK) alleviates inflammatory responses via a negative feedback mechanism. However, the contribution and
The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS
Journal of medicinal chemistry, 56(23), 9683-9692 (2013-11-08)
Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance in many human cancers. Consequently, Mer is a promising novel cancer therapeutic target. A structure-based drug design approach using a pseudo-ring replacement strategy
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