KPT-9274
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.
KPT-9274是一种口服有效的PAK4选择性变构抑制剂[1][2][3].
P21蛋白(Cdc42/Rac)活化激酶4(PAK4)是一种丝氨酸/苏氨酸蛋白激酶,属于PAK家族,PAK家族也是Rac1和Cdc42的效应蛋白.PAK4是丝状伪足形成的介质,可稳定β-连环蛋白的转录活性,参与几种实体瘤的疾病进展[1][2][3].
KPT-9274是一种口服有效的PAK4选择性抑制剂.在MDA-MB-468细胞中,KPT-9274具有抗肿瘤活性,其IC50值为0.12 μM.KPT-9274减少PAK4蛋白和细胞周期(β-连环蛋白和细胞周期蛋白D1)\细胞迁移(丝切蛋白)\自噬(AMPK)以及细胞凋亡(胱天蛋白酶和PARP裂解)的关键下游效应蛋白[1].在RCC细胞中,KPT-9274呈剂量依赖性地抑制细胞活力[2].在AML细胞系中,KPT-9274(1 nM ~ 10 μM)呈剂量和时间依赖性地抑制细胞增殖,并下调PAK4的蛋白与mRNA表达[3].
在接种MDA-MB-231或MDA-MB-468细胞的小鼠中,口服给予KPT-9274,每天1次(5 或7天/周),没有显著毒性.此外,KPT-9274诱导的最大TGI值分别为~ 55%和~ 70%[1].在皮下异种移植小鼠模型中,KPT-9274抑制RCC生长[2].在人AML白血病异种移植模型中,KPT-9274(150 mg/kg)显著地抑制肿瘤生长,阻止MV4-11细胞侵袭并延长总生存期[3].
参考文献：
[1]. Senapedis W, George R, McCauley D, et al. Preclinical Evaluation of Novel PAK4 Allosteric Modulators Against Triple Negative Breast Cancer.
[2]. Aboud OA, Senapedis W, Landesman Y, et al. Inhibition of PAK4 attenuates renal cell carcinoma (RCC) growth.
[3]. Mitchell S, Orwick S, Cannon M, et al. In Vitro and In Vivo Anti-Leukemic Effects of KPT-9274, a Reported PAK4 Allosteric Modulator, in Acute Myeloid Leukemia: Promising Results Justifying Further Development in This Disease. 57th Annual Meeting & Exposition. Orlando, FL December 5-8, 2015.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 610.62 |
| Cas No. | 1643913-93-2 |
| Formula | C35H29F3N4O3 |
| Solubility | ≥22.45 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | (1Z,2E)-3-(6-aminopyridin-2-yl)-N-((5-(4-(4,4-difluoropiperidine-1-carbonyl)phenyl)-7-(4-fluorophenyl)benzofuran-2-yl)methyl)acrylimidic acid |
| SDF | Download SDF |
| Canonical SMILES | FC1=CC=C(C2=CC(C3=CC=C(C(N4CCC(F)(F)CC4)=O)C=C3)=CC5=C2OC(C/N=C(O)/C([H])=C([H])/C6=NC(N)=CC=C6)=C5)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
- 批次:
化学结构
