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BLZ945

现货
Catalog No.
B4899
CSF-1R激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 3,000.00
现货
100mg
¥ 6,800.00
现货

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Background

BLZ945, also named as 4-[2((1R,2R)-2-Hydroxycyclohexylamino)-benzothiazol-6-yloxyl]-pyridine- 2-carboxylic acid methylamide , is a small molecule inhibitor of CSF-1R kinase with IC50 value of 1.2 nM. [2]
CSF-1R is the receptor for macrophage colony stimulating factor (M-CSF) which mediates the biological effects of this cytokine. The main biological effects of CSF-1R signaling are differentiation, proliferation, migration and survival of precursor macrophages and osteoclasts from the monocytic lineage [1].  
BLZ945 has the potential to treat an array of diseases associated with normal and deregulated function of precursor macrophages and osteoclasts from the monocytic lineage. [14C]BLZ945 metabolites were kinetically and structurally characterized from an in vitro across species comparison study using human hepatocytes and microsomes. Both compounds BLZ945 and M9 have significant anti-proliferative activity against the M-CSF dependent cell line MNFS-60 with EC50 of 71 and 140 mM, respectively. The biotransformation of BLZ945 in human liver micro-omes and recombinant cytochromes occurred predominantly via oxidative routes with also a secondary reductive pathway. [2]
BLZ945 decreased the growth of malignant cells in the mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis. BLZ945 prevented tumor progression in the keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis. [3]
References:
[1]. Stanley ER, Berg KL, Einstein DB et al. Biology and action of colony--stimulating factor-1. Mol Reprod Dev. 1997 Jan;46(1):4-10.
[2]. Krauser JA, Jin Y, Walles M et al. Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite. Xenobiotica. 2015 Feb;45(2):107-23.
[3]. Strachan DC, Ruffell B2, Oei Y et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec 1;2(12):e26968.

文献引用

1. Saha D, Martuza RL, Rabkin SD. "Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade". Cancer Cell. 2017 Aug 14;32(2):253-267.e5. PMID:28810147

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt398.48
Cas No.953769-46-5
FormulaC20H22N4O3S
Solubility≥19.9mg/mL in DMSO
Chemical Name4-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-5-yl)oxy)-N-methylpicolinamide
SDFDownload SDF
Canonical SMILESO=C(NC)C1=NC=CC(OC2=CC3=C(N=C(N[C@@H]4CCCC[C@H]4O)S3)C=C2)=C1
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

BMDM细胞系

制备方法

在DMSO中的溶解度大于19.9 mg/mL。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

6.7 ~ 6700 nM;96小时

实验结果

在BMDM细胞系中,BLZ945特异性地抑制CSF-1依赖性增殖 (EC50 = 67 nM),同时减少CSF-1R磷酸化。

动物实验 [2]:

动物模型

MMTV-PyMT转基因雌性小鼠

给药剂量

200 mg/kg;口服给药;每天1次,持续16天

实验结果

在MMTV-PyMT转基因雌性小鼠中,BLZ945减少肿瘤和肝脏中的巨噬细胞,但对肺巨噬细胞,循环单核细胞以及肿瘤细胞增殖无影响。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L, Quail DF, Olson OC, Quick ML, Huse JT, Teijeiro V, Setty M, Leslie CS, Oei Y, Pedraza A, Zhang J, Brennan CW, Sutton JC, Holland EC, Daniel D, Joyce JA. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat Med. 2013 Oct;19(10):1264-72.

[2]. Strachan DC, Ruffell B2, Oei Y et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013 Dec 1;2(12):e26968.

质量控制

化学结构

BLZ945

相关生物数据

CORM-3