UNC2025

UNC2025 is a potent, ATP-competitive, highly orally active and BBB-permeable Mer/Flt3 inhibitor with IC₅₀ values of 0.74 nM and 0.8 nM, respectively. UNC2025 is >45-fold selectivity for MERTK relative to Axl (IC₅₀= 122 nM; K_i = 13.3 nM). UNC2025 exhibits an excellent PK properties, and can be used for the investigation of acute leukemia^[1][2][3]. IC50 & Target:IC50: 0.74 nM (Mer); 0.8 nM (Flt3)^[1] In Vitro:UNC2025 is against FLT3, MER, AXL, TRKA, TRKC, QIK, TYRO3, SLK, NuaK1, KIT and Met with IC₅₀ values of 0.35 nM, 0.46 nM, 1.65 nM, 1.67 nM, 4.38 nM, 5.75 nM, 5.83 nM, 6.14 nM, 7.97 nM , 8.18 nM and 364 nM, respectively^[1].
UNC2025 (0-60 nM; 1 hour) mediates potent inhibition of Mer phosphorylation with an IC₅₀ of 2.7 nM in 697 B-ALL cells^[1].
UNC2025 (0-60 nM; 1 hour) results in decreased phosphorylation of Flt3 with an IC₅₀ of 14 nM in Flt3-ITD positive Molm-14 acute myeloid leukemia cells^[1].
UNC2025 (3 nM-3 μM; 1 hour) decreases p-MEK, p-AXL, p-TYRO3 expression as a concentration manner in 32D Cells^[1].
UNC2025 (14 nM-10 μM; 48 hours) inhibits MERTK signaling and colony-forming potential in a MERTK-expressing patient sample with a 20-fold difference in sensitivity of MERTK-expressing leukemia blasts relative to normal cord or marrow blood mononuclear cells^[2].
UNC2025 (25-300 nM; 1 hour) mediates potent and dose-dependent decreases in MERTK phosphorylation/activation in both cell lines and inhibition of MERTK correlated with decreased phosphorylation of previously reported MERTK-dependent signaling components STAT6, AKT, and ERK1/2^[2].
In Vivo:UNC2025 (intravenous injection or oral adminstration; 3 mg/kg) exhibits an excellent PK properties: low clearance (9.2 mL/min kg), longer half-life (3.8 h), and high oral exposure (100%), it shows T_max, C_max, and AUClast 0.50 hour, 1.6 μM, and 9.2 h μM, respectively^[2].
UNC2025 (orally adminstration; 50 or 75 mg/kg; 34 and 70 days) mediates a statistically significant dose-dependent reduction in tumor burden relative to vehicle. mediates dose-dependent increases in median survival from 26 days after initiation of treatment in vehicle-treated mice, to 34 and 70 days in mice treated with 50 or 75 mg/kg UNC2025, respectively^[2].