Pexidartinib (PLX3397)
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.
集落刺激因子1(CSF1)是参与组织巨噬细胞招募和活化的关键细胞因子,通过结合高亲和力的受体酪氨酸激酶CFMS/CSF1受体发挥以上效应.Pexidartinib (PLX3397)是CSF-1R的抑制剂,可以穿越血脑屏障.
体外实验:PLX3397强烈衰减由B16F10黑色素瘤驱动的巨噬细胞的全身和局部积累,不影响Gr-1+骨髓衍生的抑制性细胞[1].
在体实验:野生型的C57小鼠原位注射GL261细胞,使用PLX3397化合物口服2周后,对照组的肿瘤显示广泛的小胶质细胞浸润.在PLX3397处理的动物中,肿瘤中Iba1-阳性细胞的数量显著减少[2].
临床试验:在Ib期试验中,晚期实体瘤患者每周使用紫杉醇和口服不断升级剂量的PLX3397,建立PLX3397的RP2D.这项研究将支持I-SPY-2新辅助化疗的乳腺癌实验中PLX3397-紫杉醇组合治疗的进一步发展.
参考文献:
[1] Sluijter M, van der Sluis TC, van der Velden PA, Versluis M, West BL, van der Burg SH, van Hall T. Inhibition of CSF-1R supports T-cell mediated melanoma therapy. PLoS One. 2014 Aug 11;9(8):e104230.
[2] Coniglio SJ, Eugenin E, Dobrenis K, Stanley ER, West BL, Symons MH, Segall JE. Microglial stimulation of glioblastoma invasion involves epidermal growth factor receptor (EGFR) and colony stimulating factor 1 receptor (CSF-1R) signaling. Mol Med. 2012 May 9;18:519-27.
- 1. Jinchao Gao, Qingxiang Song, et al. "Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function." Nat Nanotechnol. 2024 Mar;19(3):376-386. PMID: 38158436
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- 3. Nina M. Dräger, Sydney M. Sattler, et al. "A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states." Nat Neurosci. 2022 Sep;25(9):1149-1162. PMID: 35953545
- 4. Komohara Y, Noyori O, et al. "Potential anti-lymphoma effect of M-CSFR inhibitor in adult T-cell leukemia/lymphoma." J Clin Exp Hematop. 2018;58(4):152-160. PMID: 30541986
- 5. Yu R, Jin H, et al. "Inhibition of the CSF-1 receptor sensitizes ovarian cancer cells to cisplatin." Cell Biochem Funct. 2018 Jan 25. PMID: 29372560
- 6. Wang C, Yeo S, et al. "Autophagy gene FIP200 in neural progenitors non-cell autonomously controls differentiation by regulating microglia." J Cell Biol. 2017 Jun 20. pii: jcb.201609093. PMID: 28634261
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 417.81 |
Cas No. | 1029044-16-3 |
Formula | C20H15ClF3N5 |
Solubility | insoluble in EtOH; insoluble in H2O; ≥20.9 mg/mL in DMSO |
Chemical Name | 5-((5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)pyridin-2-amine |
SDF | Download SDF |
Canonical SMILES | ClC(C=N1)=CC2=C1NC=C2CC3=CN=C(NCC4=CN=C(C(F)(F)F)C=C4)C=C3 |
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 |
SK-N-SH细胞 |
溶解方法 |
该化合物在DMSO中的溶解度大于20.9 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。 |
反应条件 |
IC50: 10 μM |
应用 |
Pexidartinib微弱抑制SK-N-SH细胞的生长,IC50为10 μM。PLX3397对MDA-MB-231人肿瘤细胞异种移植物的生长几乎没有影响。 |
动物实验 [1,2]: | |
动物模型 |
B16F10黑色素瘤细胞异种移植的C57BL/6小鼠,携带MDA-MB-468人乳腺肿瘤细胞异种移植物的雌性裸鼠。 |
给药剂量 |
口服,每日剂量约45 mg/kg |
应用 |
Pexidartinib主要影响F4/80+ Ly6C-血液巨噬细胞,并且强烈降低F4/80+Ly6C+'炎性'单核细胞的CSF-1R表达水平。口服给药PLX3397可以防止破骨细胞的增加和骨骼的损失。 |
注意事项 |
由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。 |
References: [1] West B L, DeNardo D G, Tsai J, et al. Efficacy of the selective CSF-1R kinase inhibitor PLX3397 in mouse models of tumor growth and bone metastasis[J]. 2010. [2] Sluijter M, van der Sluis T C, van der Velden P A, et al. Inhibition of CSF-1R supports T-cell mediated melanoma therapy[J]. PloS one, 2014, 9(8): e104230. |
质量控制和MSDS
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