UNC569 is a novel small molecule Mer tyrosine kinase inhibitor with potent activity against Mer (Mer IC50 = 2.9nM)[1].
In vitro, UNC569 (0, 400, 800, 1000, 1200, 1400, 1600, 1800, and 2000nM; 48h) reduces proliferation and induces apoptosis in acute lymphoblastic leukemia (ALL) cells[1]. In macrophages derived from THP-1 cells, UNC569 (5μM; 48h) significantly inhibits Gas-6-induced MerTK phosphorylation and Akt activation[2]. In the presence and absence of exogenous galectin-3, UNC569 (5μM; 48h) strongly inhibited microglial phagocytosis of bacteria, without affecting microglial viability[3].
In vivo, In a mouse animal experiment, the MerTK inhibitor UNC569 (60, 100 and 150mg/kg or 100mg/kg; 14 days or 15, 17, 18.5 and 20h; p.o.) impaired the phagocytic function of the retinal pigment epithelium (RPE), leading to accumulation of photoreceptor outer segments (POS) and increased phagosomes and phagolysosomes in the RPE[4].
References:
[1] Christoph S, Deryckere D, et al. UNC569, a novel small-molecule mer inhibitor with efficacy against acute lymphoblastic leukemia in vitro and in vivo. Mol Cancer Ther. 2013 Nov;12(11):2367-77.
[2] Pastore M, Caligiuri A, Raggi C, et al. Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators. JHEP Rep. 2022 Feb 1;4(4):100444.
[3] Cockram TOJ, Puigdellívol M, Brown GC. Calreticulin and Galectin-3 Opsonise Bacteria for Phagocytosis by Microglia. Front Immunol. 2019 Nov 12;10:2647.
[4] Sayama A, Okado K, Nakamura K, et al. UNC569-induced Morphological Changes in Pigment Epithelia and Photoreceptor Cells in the Retina through MerTK Inhibition in Mice. Toxicol Pathol. 2018 Feb;46(2):193-201.
UNC569是一种新型小分子Mer酪氨酸激酶抑制剂，对Mer具有强效抑制作用（Mer IC50=2.9nM）[1]。
在体外实验中，UNC569（0, 400,800, 1000, 1200, 1400, 1600, 1800和2000Nm; 48小时）可减少急性淋巴细胞白血病（ALL）细胞的增殖并诱导其凋亡[1]。在由THP-1细胞衍生的巨噬细胞中，UNC569（5μM; 48小时）显著抑制Gas-6诱导的MerTK磷酸化和Akt激活[2]。在有无外源性半乳糖凝集素-3的情况下，UNC569（5μM; 48小时）显著抑制小胶质细胞对细菌的吞噬作用，但不影响小胶质细胞的活性[3]。
在体内实验中，在小鼠动物实验中，MerTK抑制剂UNC569（60, 100和150mg/kg; 14天; 口服）损害了视网膜色素上皮细胞（RPE）的吞噬功能，导致感光细胞外节段（POS）的积累和RPE中吞噬体及吞噬溶酶体的增加[4]。