| 名称 | Sotuletinib |
| 描述 | Sotuletinib (BLZ945) is a CSF-1R inhibitor, a highly selective, brain-penetrant CSF-1R inhibitor (IC50 = 1 nM, with 1000-fold selectivity over other kinases), with oral activity, used for microglia depletion and tumor and neurological disease research. |
| 细胞实验 | Cell growth rate is determined using the MTT cell proliferation kit. Briefly, cells are plated in triplicate in 96-well plates: 1,000 cells per well for glioma cell lines, 5 x 1,000 cells per well for BMDM and CRL-2467, and 2.5 x 1,000 cells per well for HUVEC and HBMEC cell lines. For all experiments, media is changed every 48 h. Cells are grown in the presence or absence of 6.7–6,700 nM of BLZ945, or 8 μg/mL of CSF-1R neutralizing antibody. BMDM and CRL-2467 cells were supplemented with 10 ng/mL and 30 ng/ mL recombinant mouse CSF-1, respectively. Reduction of the MTT substrate is detected by colorimetric analysis using a plate reader as per the manufacturer's protocol, and measured at 595 nm and 750 nm on a spectraMax 340pc plate reader.(Only for Reference) |
| 激酶实验 | Inhibition of biochemical TrkA, TrkB and TrkC: TrkA and TrkC biochemical assays are carried out by HTRF method. The reaction mixtures contains 1 μM peptide substrate, 1 μM ATP, and either 1.8 nM TrkA or 34 nM TrkC in the reaction buffer (50 mM HEPES pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.01% BSA, 2.5 mM DTT and 0.1 mM Na3VO4) at a final volume of 10 μL. All reactions are carried out at room temperature in white ProxiPlate? 384-well Plus plates and are quenched with 5 μL of 0.2 mM EDTA at 60 min. Five μL of the detection reagents (2.5 ng PT66K and 0.05 μg SAXL per well) are added, the plates are incubated at room temperature for 1 h and then read in EnVision reader. Compounds are diluted into assay mixture (final DMSO 0.5%), and IC50 values are determined by 12-point (from 50 to 0.000282 μΜ) inhibition curves in duplicate under the assay conditions. TrkB biochemical assay is carried out by caliper microfluidic method. The reaction mixtures contained 1 μM peptide substrate, 10 μM ATP, and 2 nM TrkB in a reaction buffer containing 100 mM HEPES, pH 7.5, 5 mM MgCl2, 0.01% Triton X-100, 0.1% BSA, 1 mM DTT, 10 μΜNa3VO4, and 10 μΜBeta-Glycerophosphate. The reactions are carried out at room temperature for 3 hrs, and the products are determined by Caliper EZ-reader. Compounds are diluted into assay mixture (final DMSO 1%), and IC50 values are determined by 12-point (from 50 to 0.000282 μΜ) inhibition curves in duplicate under the assay conditions. |
| 体外活性 | 方法：在TGCT细胞系（Si-TGCT-1、-2、-3、-4）及对照细胞Bewo和MDA-MB-231中，以0–1000 μM的Sotuletinib孵育96小时，通过MTS法检测细胞活力。
结果：Sotuletinib抑制TGCT细胞增殖，诱导凋亡并增加BAX/BCL-2比值，其IC50值随CSF1R表达水平变化。[1] |
| 体内活性 | 方法：在雄性NSG小鼠ccRCC模型中，Sotuletinib每日口服灌胃给药，剂量200 mg/kg，溶于20% DMSO，连续三周。[2]
结果：与对照组相比，Sotuletinib组肿瘤体积显著缩小，肿瘤组织Ki67表达降低，M2型巨噬细胞（CD68+CD163+）比例减少。
方法：在4T1荷瘤小鼠模型中，Sotuletinib（BLZ-945）通过尾静脉注射给药，剂量为1.75 mg/kg，每3天一次，溶剂为PBS，联合660 nm激光照射。
结果：该治疗组肿瘤生长显著受抑，肿瘤组织中M2型肿瘤相关巨噬细胞比例降至约19.86%，脾脏中细胞毒性T淋巴细胞比例达约39.36%。[3]
方法：在雄性Wistar Han大鼠中，Sotuletinib以150 mg/kg/day剂量每日口服灌胃给药，溶剂为醋酸钠-甲基纤维素溶液，连续给药16天后停药。
结果：给药期间ALT升高，停药后迅速恢复至对照水平，且未伴随肝损伤或miR-122升高。[4] |
| 存储条件 | Keep away from direct sunlight,Keep away from moisture,Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 257 mg/mL (644.95 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (12.55 mM), Sonication is recommended.
Ethanol : 3 mg/mL (7.53 mM), Heating is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | Sotuletinib | Inhibitor | inhibit | CSF-1R | CSF1R | CSF-1 receptor | colony stimulating factor 1 receptor | c-Fms | cFms | BLZ-945 | BLZ 945 |
| 相关产品 | Onatasertib | AZD7507 | Cerdulatinib hydrochloride | GW786034B | PLX647 | GW2580 | Tandutinib | Dovitinib | c-Fms-IN-13 | Pexidartinib | PLX5622 | c-Fms-IN-3 |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 临床失败化合物库 | 激酶抑制剂库 | 高选择性抑制剂库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |