UNC5293 is a potent, orally available and highly MERTK-selective inhibitor with Ki of 190 pM. UNC5293 inhibits MERTK ( IC 50 =0.9 nM) and is more selective over Axl, Tyro3 and Flt3. UNC5293 exhibits excellent mouse PK properties and is used for bone marrow leukemia research [1].

UNC5293 demonstrates selective inhibition of its target in cell-based assays, effectively inhibiting MERTK phosphorylation in human B-cell acute lymphoblastic leukemia (B-ALL) cultures with an IC50 of 9.4 nM. However, it shows weaker activity against FLT3 in the SEM B-ALL cell line, with an IC50 of 170 nM [1].

UNC5293 administered orally at a dosage of 120 mg/kg as a single dose significantly inhibits MERTK in vivo within orthotopic 697 B-ALL mouse xenograft models [1]. At a lower dosage of 3 mg/kg via oral gavage, UNC5293 demonstrates favorable pharmacokinetic attributes in mice, including a half-life of 7.8 hours, 58% oral bioavailability, a maximum concentration (C max) of 9.2 μM, and an area under the curve (AUC) of 2.5 h*μM [1].