UNC5293 是一种 MERTK 选择性的有效抑制剂 (Ki=190 pM)。UNC5293 抑制 MERTK (IC50=0.9 nM)，对 Axl、Tyro3 和 Flt3 更具选择性。UNC5293 表现出优异的小鼠药代动力学特性，并可以被用于骨髓白血病研究。
UNC5293 is a MERTK-selective and potent inhibitor (Ki=190 pM). UNC5293 inhibits MERTK (IC50=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 provides selective target inhibition in cell-based assays. In cultures of the human B-cell acute lymphoblastic leukemia (B-ALL) cell line, UNC5293 inhibits phosphorylation of MERTK with an IC50 of 9.4 nM. In the SEM B-ALL cell line, UNC5293 is less potent against FLT3, with an IC50 of 170 nM[1].
UNC5293 (oral administration; 120 mg/kg; single dose) effectively inhibit MERTK in vivo in orthotopic 697 B-ALL mice xenografts[1].UNC5293 (oral gavage; 3 mg/kg; single dose) has excellent mouse PK properties (7.8 h half-life and 58% oral bioavailability), and the Cmax and AUClast are 9.2 μM and 2.5 h*μM, respectively[1].
[1]. Hongchao Zheng, et al. UNC5293, a potent, orally available and highly MERTK-selective inhibitor. Eur J Med Chem. 2021 May 17;220:113534.
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