PF-3644022
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.
PF-3644022是促分裂原活化蛋白激酶(MAPK)活化蛋白激酶2(MK2)的有效选择性抑制剂,Ki值为3 nM[1]
PF-3644022是第一个急性和慢性炎症模型的口服MK2抑制剂.PF-3644022可逆的ATP竞争性抑制MK2酶的活性,与人的200种激酶相比具有较好的选择性[1].
在人U937单核细胞系或外周血单核细胞中,PF-3644022有效抑制TNF生成,IC50值为160 nM.在LPS刺激的人全血中,PF-3644022阻断TNF和IL-6的生成,IC50值分别为1.6和10.3 μM.在U937细胞和血液中,肿瘤坏死因子(TNF)的抑制与磷酸化热休克蛋白27的抑制密切相关,热休克蛋白27是MK2活性的目标生物标志物[1].
在LPS诱导的TNF大鼠模型中,PF-3644022在慢性炎症模型中的疗效与维持Cmin高于EC50密切相关.在慢性链球菌细胞壁诱导的关节炎模型和大鼠急性LPS诱导的TNF模型中,PF-3644022具有有效的口服活性和良好的药代动力学参数[1].
参考文献:
1. Mourey RJ, Burnette BL, Brustkern SJ et al. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. doi: 10.1124/jpet.110.166173. Epub 2010 Mar 17.
- 1. Leonie Ratz, Chiara Brambillasca, et al. "Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer." Breast Cancer Res. 2022 Jun 17;24(1):41. PMID: 35715861
- 2. Leonie Ratz, Chiara Brambillasca, et al. "EZH2 Inhibition Sensitizes BRCA1-Deficient Breast Cancer to Synthetic Lethal Therapy with ATM Inhibitors." Research Square. June 15th, 2021.
Physical Appearance | Yellow solid |
Storage | Store at -20°C |
M.Wt | 374.46 |
Cas No. | 1276121-88-0 |
Formula | C21H18N4OS |
Solubility | <14.98mg/ml in DMSO |
Chemical Name | (R)-10-methyl-3-(6-methylpyridin-3-yl)-11,12-dihydro-10H-[1,4]diazepino[5',6':4,5]thieno[3,2-f]quinolin-8-ol |
SDF | Download SDF |
Canonical SMILES | CC1=NC=C(C2=NC(C=CC(S3)=C4C5=C3C(O)=N[C@](CN5)([H])C)=C4C=C2)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。 |