UNC569

UNC569 is a potent, reversible, ATP-competitive and orally active Mer kinase inhibitor with an IC₅₀ of 2.9 nM and a K_i of 4.3 nM. UNC569 also inhibits Axl and Tyro3 with IC₅₀s of 37 nM and 48 nM, respectively. UNC569 can be used for acute lymphoblastic leukemia (ALL) and atypical teratoid/rhabdoid tumors research^[1][2] IC50 & Target: IC50: 2.9 nM (Mer), 37 nM (Axl), 48 nM (Tyro3)^[1] Ki: 4.3 nM (Mer)^[1] In Vitro: UNC569 (24 hours) induces apoptosis in ALL cell lines, and increases the levels of cleaved Caspase 3 and cleaved PARP^[2].
UNC569 (1 µM; 1.5 hours) treatment effectively inhibit the activation of Mer and downstream signaling, including the PI3K/AKT and MAPK/ERK pathways^[2].
UNC569 (1 hour) inhibits Mer phosphorylation levels with IC50 values of 141 nM and 193 nM in human B-ALL (acute lymphoblastic leukemia) 697 and Jurkat cell lines, respectively^[1][2]. In Vivo: The in vivo pharmacokinetic properties of UNC569 (3 mg/kg) are also assessed in mice via both intravenous (IV) and oral (PO) administration. UNC569 has low systemic clearance (19.5 mL/min/kg), high volume of distribution (V_ss of 5.83 L/kg), and good oral bioavailability (57%)^[1].
Leukemic zebrafish are treated continuously for 2 weeks by immersion in 4 µM UNC569. the result shows that UNC569 induces more than 50% reduction in tumor burden compared with vehicle- and mock-treated fish^[2].