Pexmetinib (ARRY-614)
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.
Pexmetinib(ARRY-614)是细胞因子合成的有效抑制剂,通过对 p38促分裂原活化蛋白激酶和Tie2/Tek受体酪氨酸激酶的双重抑制(MAPK)来发挥作用。ARRY-614体外抑制Tie2和p38促分裂原活化蛋白激酶的IC50值分别是1000 ng/mL和100 ng/mL[1,2]。
p38是一组促分裂原活化蛋白激酶。MAPKs通过在亚结构域VIII的Thr-Xaa-Tyr基序中酪氨酸和苏氨酸位点的双重磷酸化而激活。数据表明,p38蛋白可能介导细胞核信号[3]。
ARRY-614针对细胞中MAPK和Tie2/Tek受体酪氨酸激酶发挥功能。在原代人骨髓基质细胞中,ARRY-614抑制基础的细胞因子,IC50值范围为50-100 nM [4]。
在剂量递增或扩张实验中,45个病人每日一次或两次接受ARRY-614治疗。ARRY-614减少骨髓中循环生物标志物的水平和p38蛋白的活化[1]。在离体刺激的人全血中,ARRY-614抑制LPS诱导的细胞因子,IC50值范围为50-120 nM。ARRY-614抑制接种SEA或LPS的小鼠释放IL-6,ED50值小于10 mg/kg。 ARRY-614与lenalidomide共同作用时,会抑制体内的促炎细胞因子和肿瘤生长,与单独的任一药剂相比,具有更高的效力[4]。
参考文献:
[1]. Garcia-Manero G, Khoury HJ, Jabbour E, et al. A phase I study of oral ARRY-614, a p38 MAPK/Tie2 dual inhibitor, in patients with low or intermediate-1 risk myelodysplastic syndromes. Clinical Cancer Research, 2015, 21(5): 985-994.
[2]. Wollenberg LA, Corson DT, Nugent CA, et al. An exploratory, randomized, parallel-group, open-label, relative bioavailability study with an additional two-period crossover food-effect study exploring the pharmacokinetics of two novel formulations of pexmetinib (ARRY-614). Clinical pharmacology: advances and applications, 2015, 7: 87.
[3]. Raingeaud J, Whitmarsh AJ, Barrett T, et al. MKK3-and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Molecular and cellular biology, 1996, 16(3): 1247-1255.
[4]. Winski S, Humphries M, Yeh T, et al. Activity of ARRY-614, an inhibitor of p38 map kinase and angiogenic targets, in hematologic malignancies. Cancer Research, 2009, 69(9 Supplement): 331-331.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 556.64 |
Cas No. | 945614-12-0 |
Formula | C31H33FN6O3 |
Solubility | insoluble in H2O; ≥107.6 mg/mL in DMSO; ≥113 mg/mL in EtOH |
Chemical Name | 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(5-fluoro-2-((1-(2-hydroxyethyl)-1H-indazol-5-yl)oxy)benzyl)urea |
SDF | Download SDF |
Canonical SMILES | CC1=CC=C(N2C(NC(NCC3=CC(F)=CC=C3OC4=CC=C5C(C=NN5CCO)=C4)=O)=CC(C(C)(C)C)=N2)C=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。 |
质量控制和MSDS
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