Methanone, (2,6-dimethyl-4-pyridinyl)[4-[7-(trans-4-hydroxycyclohexyl)-2-[[(1S)-1-methylbutyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1-piperidinyl]-

Biological Activity

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].

References

[1]. Hongchao Zheng, et al. UNC5293, a potent, orally available and highly MERTK-selective inhibitor. Eur J Med Chem. 2021 May 17;220:113534.