UNC569
目录号 : GC18308
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）。
Cas No.:1350547-65-7
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
Cell lines | Jurkat or 697 cells |
Preparation Method | Jurkat or 697 cells were plated at a density of 3×10⁵ cells/ml and treated with UNC569 (0, 400, 800, 1000, 1200, 1400, 1600, 1800 and 2000nM) for 48h. Alternatively, cells were treated with UNC569 for 24h, then harvested and cultured in fresh medium containing UNC569 or vehicle only for an additional 24h. Cells were collected by centrifugation at 240g for 5min. Cell pellets were resuspended in PBS containing 1µM YO-PRO-1 and 1.5µM propidium iodide. Samples were incubated for 15min, and fluorescence was detected using a FC500 flow cytometer and analyzed with CXP data analysis software. |
Reaction Conditions | 0, 400, 800, 1000, 1200, 1400, 1600, 1800 and 2000nM; 48h |
Applications | UNC569 reduces proliferation and induces apoptosis in acute lymphoblastic leukemia (ALL) cells. |
| Animal experiment [2]: | |
Animal models | Male BALB/c AnNCrlCrlj mice |
Preparation Method | UNC569 was administered orally once daily at doses of 60, 100, and 150mg/kg for 14 days. Animals receiving 0.5 w/v% methyl cellulose in the same manner served as the control group. During the experiment, light was introduced into the room at 7:00, and dosing was conducted at 10:30. The first day of dosing was defined as day 1. Animals were euthanized by exsanguinations under isoflurane anesthesia and necropsied at 10:30 on day 15. Eyes were removed from all animals. The right eyes were fixed in Davidson’s fixative, embedded in paraffin, and prepared as histopathological specimens, which were stained with hematoxylin and eosin (HE) for light microscopy. The left eyes were fixed in 2.5% glutaraldehyde, postfixed in 2% osmium tetroxide, and embedded in resin. Semithin sections were stained with toluidine blue (TB) for light microscopy, and ultrathin sections were stained with uranyl acetate and lead for electron microscopy. |
Dosage form | 60, 100 and 150mg/kg; 14 days; p.o. |
Applications | In a mouse animal experiment, the MerTK inhibitor UNC569 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. |
References: | |
| Cas No. | 1350547-65-7 | SDF | |
| 化学名 | 1-[(trans-4-aminocyclohexyl)methyl]-N-butyl-3-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine | ||
| Canonical SMILES | CCCCNC1=NC=C2C(N(C[C@H]3CC[C@H](N)CC3)N=C2C4=CC=C(F)C=C4)=N1 | ||
| 分子式 | C22H29FN6 | 分子量 | 396.5 |
| 溶解度 | DMF: 2.5 mg/ml,DMF:PBS (pH 7.2) (1:4): 0.2 mg/ml,DMSO: 0.2 mg/ml,Ethanol: 2 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5221 mL | 12.6103 mL | 25.2207 mL |
| 5 mM | 504.4 μL | 2.5221 mL | 5.0441 mL |
| 10 mM | 252.2 μL | 1.261 mL | 2.5221 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet