BLZ945
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
BLZ945,又名4-[2((1R,2R)-2-羟基环己胺基)-苯并噻唑-6-氧]-吡啶-2-羧酸甲酰胺,是一种CSF-1R激酶的小分子抑制剂,IC50值为1.2 nM.[2]
CSF-1R是巨噬细胞集落刺激因子(M-CSF)的受体,可介导该细胞因子的生物学效应.CSF-1R信号的主要生物学功能是前体巨噬细胞和单核细胞谱系破骨细胞的分化\增殖\迁移和存活[1].
BLZ945对与正常和功能失调的前体巨噬细胞和单核细胞谱系破骨细胞相关的一系列疾病有治疗潜力.在使用人类肝细胞和微粒体的体外跨物种比较研究中,[14C]BLZ945代谢物可在动力学和结构上被检出.BLZ945和M9对M-CSF依赖的细胞系MNFS-60均具有显著的抗增殖活性,EC50值分别为71和140 mM.BLZ945对人类肝脏微粒体和重组细胞色素的生物转化主要通过氧化途径和二次还原途径进行.[2]
在小鼠乳腺肿瘤病毒驱动的多瘤病毒中间T抗原(MMTV-PyMT)乳腺癌模型中,BLZ945可降低恶性细胞生长.在表达角蛋白14的人类乳头瘤病毒16型(K14-HPV-16)转基因宫颈癌模型中,BLZ945可阻止肿瘤进程.[3]
参考文献：
[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.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 398.48 |
| Cas No. | 953769-46-5 |
| Formula | C20H22N4O3S |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥19.9 mg/mL in DMSO |
| Chemical Name | 4-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-5-yl)oxy)-N-methylpicolinamide |
| SDF | Download SDF |
| Canonical SMILES | O=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 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验 [1]: | |
|
细胞系 |
BMDM细胞系 |
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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]: | |
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动物模型 |
MMTV-PyMT转基因雌性小鼠 |
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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。 |
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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。 |
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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. |
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质量控制和MSDS
- 批次:
化学结构
相关生物数据
