UNC2881

UNC2881 is an orally active and specific Mer kinase inhibitor, inhibits steady-state Mer kinase phosphorylation with an IC₅₀ value of 22 nM. UNC2881 shows additional inhibition against Axl and Tyro with IC₅₀s of 360 nM and 250 nM, respectively. UNC2881 potently inhibits collagen-induced platelet aggregation, can be used for pathologic thrombosis research^[1]. IC50 & Target: IC50: 4.3 nM (Mer), 360 nM (Axl), 250 nM (Tyro)^[1] In Vitro: UNC2881 (compound 23) (0-1000 nM; 1 h) block ligand-stimulated activation of a chimeric EGFR-MerTK. UNC2881 also inhibits endogenous Mer tyrosine kinase activation in acute lymphoblastic leukemia cells^[1].
UNC2881 (3 μM; 1 h) suppresses platelet aggregation by greater than 25% in human platelet-rich plasma in response to stimulation with fibrillar type I equine collagen^[1].
In Vivo: UNC2881 (3 mg/kg; p.o.; single dose) has high systemic clearance (94.5 mL/min/kg) and 14% oral bioavailability, displays terminal half-life of 0.80 h^[1].
UNC2881 (3 mg/kg; i.v.; injected with VSV on days -3, -2, -1, and 0) limits Mertk signaling, and promotes the antiviral immune response, reducing the viral replication of vesicular stomatitis virus (VSV) in infected mice^[2].
Pharmacokinetics of UNC2881 in mice^[1]

Route	Dose (mg/kg)	T1/2 (h)	Tmax (h)	Cmax (ng/mL)	AUClast (ng·h/mL)	CLobs (mL/min)	Vss (L/kg)	F (%)
IV	3	0.8		2609	527	94.5	1.65
PO	3		0.30	90.0	71.7			14