R428
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.
R428是一种选择性的Axl抑制剂,IC50值为14 nM。与Abl、Mer、Tyro3、InsR、EGFR、HER2和PDGFR相比,R428对Axl具有超过50倍的灵敏度。
Axl受体酪氨酸激酶通过结合维生素K依赖性蛋白growth arrest-specific 6 (Gas6)将细胞外基质信号传导到胞浆内。Axl参与多个细胞内进程,包括细胞生长、迁移、聚集和抗炎活性。
R428在低纳摩尔浓度下就可以阻断Axl的催化活性,同时抑制Axl依赖的活性,包括Akt磷酸化、细胞侵袭、促炎因子的产生。R428可以减少粒细胞巨噬细胞集落刺激因子和上皮-间质转化转录因子Snail的表达。R428还可以抑制血管生成,减少转移性肿瘤负荷,在动物异种移植模型中提高生存率。此外,R428与cisplatin协同作用可以提高肝脏微转移的抑制效率。R428可以口服给药。
参考文献:
[1]Holland SJ, Pan A, Franci C, et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolong survival in models of metastatic breast cancer. Cancer Res 2010. 70(4): 1544-1554.
- 1. Bryan J González, Haoquan Zhao, et al. "Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency." Commun Biol. 2022 Aug 2;5(1):779. PMID: 35918471
- 2. Nil Vanli, Jinghao Sheng, et al. "Ribonuclease 4 is associated with aggressiveness and progression of prostate cancer." Commun Biol. 2022 Jun 25;5(1):625. PMID: 35752711
- 3. Samuel D. Zwernik, Beau H. Adams, et al. "AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines." Mol Ther Oncolytics. 2021 Nov 11;23:447-457. PMID: 34901388
- 4. Sekyu Choi, Bing Zhang, et al. "Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence." Nature. 2021 Apr;592(7854):428-432. PMID: 33790465
- 5. Qi Bian, Joshua C. Anderson, et al. "Mesangioproliferative Kidney Diseases and Platelet-Derived Growth Factor–Mediated AXL Phosphorylation." Kidney Medicine.Available online 30 July 2021.
- 6. Afnan Abu-Thuraia, Marie-Anne Goyette, et al. "AXL confers cell migration and invasion by hijacking a PEAK1-regulated focal adhesion protein network." Nat Commun. 2020 Jul 17;11(1):3586. PMID: 32681075
- 7. McDaniel NK, Iida M, et al. "AXL Mediates Cetuximab and Radiation Resistance Through Tyrosine 821 and the c-ABL Kinase Pathway in Head and Neck Cancer." Clin Cancer Res. 2020;10.1158/1078-0432.CCR-19-3142. PMID: 32439698
- 8. Tsai KYF, Hirschi Budge KM, et al. "RAGE and AXL expression following secondhand smoke (SHS) exposure in mice." Exp Lung Res. 2019 Nov - Dec;45(9-10):297-309. PMID: 31762322
- 9. Hirschi KM, Tsai KYF, et al. "Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats." Biol Reprod. 2019 Jul 26. pii: ioz140. PMID: 31347670
- 10. Goyette MA, Cusseddu R, et al. "AXL knockdown gene signature reveals a drug repurposing opportunity for a class of antipsychotics to reduce growth and metastasis of triple-negative breast cancer." Oncotarget. 2019 Mar 12;10(21):2055-2067. PMID: 31007848
- 11. Chen F, Song Q, et al. "Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition." Am J Cancer Res. 2018 Aug 1;8(8):1466-1482. PMID: 30210917
- 12. McDaniel NK, Cummings CT, et al. "MERTK mediates intrinsic and adaptive resistance to AXL-targeting agents." Mol Cancer Ther. 2018 Aug 9. pii: molcanther.1239.2017. PMID: 30093568
- 13. Goyette MA, Duhamel S, et al. "The Receptor Tyrosine Kinase AXL Is Required at Multiple Steps of the Metastatic Cascade during HER2-Positive Breast Cancer Progression." Cell Rep. 2018 May 1;23(5):1476-1490. PMID: 29719259
- 14. Zuo Q, Liu J, et al. "AXL/AKT axis mediated-resistance to BRAF inhibitor depends on PTEN status in melanoma." Oncogene. 2018 Mar 19. PMID: 29551771
- 15. Sui L, Danzl N, et al. "Beta Cell Replacement in Mice Using Human Type 1 Diabetes Nuclear Transfer Embryonic Stem Cells. Diabetes." 2017 Sep 20. pii: db170120. PMID: 28931519
- 16. Xi Y, Kim T, et al. "Local lung hypoxia determines epithelial fate decisions during alveolar regeneration." Nat Cell Biol.2017 Aug;19(8):904-914. PMID: 28737769
- 17. Singh PK, Guest JM, et al. "Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes." JCI Insight. 2017 Feb 23;2(4):e92340. PMID: 28239662
- 18. Retallack H, Di Lullo E, et al. "Zika virus cell tropism in the developing human brain and inhibition by azithromycin." Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413. PMID: 27911847
- 19. Liu S, DeLalio LJ, et al. "AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus." Circ Res. 2016 Nov 11;119(11):1183-1189. PMID: 27650556
- 20. Tabata T, Petitt M, et al. "Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission. Cell Host Microbe." 2016 Aug 10;20(2):155-66. PMID: 27443522
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 506.64 |
Cas No. | 1037624-75-1 |
Formula | C30H34N8 |
Synonyms | R-428; R 428; BGB324; Bemcentinib |
Solubility | ≥25 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH |
Chemical Name | 1-(6,7-dihydro-5H-benzo[2,3]cyclohepta[2,4-d]pyridazin-3-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine |
SDF | Download SDF |
Canonical SMILES | C1CCN(C1)C2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76 |
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 |
MDA-MB-231细胞、4T1细胞和Hela细胞。 |
溶解方法 |
在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应时间 |
R428剂量滴定(≤10 μM);3小时 |
应用 |
R428在低纳摩尔浓度时抑制Axl,阻断Axl依赖性的活动,包括Akt的磷酸化,乳腺癌细胞侵袭和促炎细胞因子的产生。 |
动物实验[2]: | |
动物模型 |
在乳房脂肪垫接种0.5×106 4T1细胞的雌性BALB/c小鼠。 |
剂量 |
7-75 mg/kg,2次/天,19-20天;口服给药。 |
应用 |
R428口服给药后剂量依赖性地减少粒细胞巨噬细胞集落刺激因子和上皮-间质转化转录因子Snail的表达。在MDAMB-231心内和4T1原位乳腺癌转移小鼠模型中,R428减少肿瘤转移,提高存活率(中位生存,>80天,与52天相比;P<0.05)。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Holland SJ, Pan A, Franci C et al. R428, a selective small molecule inhibitor of Axl kinase, blocks tumor spread and prolongs survival in models of metastatic breast cancer. Cancer Res. 2010 Feb 15;70(4):1544-54. |
描述 | R428 (BGB324)是一种选择性的Axl抑制剂,IC50值为14 nM。 | |||||
靶点 | Axl | |||||
IC50 | 14 nM |
质量控制和MSDS
- 批次: