KPT-9274
目录号 : GC14615Orally acitve allosteric inhibitor of PAK4
Cas No.:1643913-93-2
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
KPT-9274 is a selective and orally bioavailable allosteric inhibitor of PAK4 [1][2][3].
P21 protein (Cdc42/Rac)-activated kinase 4 (PAK4) is a serine/threonine-protein kinase and a member of the PAK family of proteins which are Rac1 and Cdc42 effectors. PAK4 is a mediator of filopodia formation and stabilizes β-catenin transcriptional activity, and is involved in disease progression for several solid tumors [1][2][3].
KPT-9274 is a selective and orally bioavailable PAK4 inhibitor. In MDA-MB-468 cells, KPT-9274 showed anti-tumor activity with IC50 value of 0.12 μM. KPT-9274 reduced PAK4 protein and the key downstream effectors of cell cycle (β-catenin, cyclin D1), cell migration (cofilin), autophagy (AMPK) and apoptosis (Caspase and PARP cleavage) [1]. In RCC cells, KPT-9274 dose-dependently inhibited cell viability [2]. In AML cell lines, KPT-9274 (1 nM-10 μM) inhibited cell proliferation in a dose-and time- dependent way and reduced protein and mRNA expression of PAK4 [3].
In mice inoculated with MDA-MB-231 or MDA-MB-468 cells, KPT-9274 were given orally once daily (5 or 7 days/week) without major toxicity. KPT-9274 induced a maximum TGI of ~55% and ~70% in MDA-MB-231 and MDA-MB-468 mice, respectively [1]. In subcutaneous xenograft mouse models, KPT-9274 inhibited RCC growth [2]. In human AML leukemia xenograft model, KPT-9274 (150 mg/kg) significantly inhibited tumor growth, prevented invasion of MV4-11 cells, and improved overall survival [3].
References:
[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.
Cas No. | 1643913-93-2 | SDF | |
化学名 | (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 | ||
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 | ||
分子式 | C35H29F3N4O3 | 分子量 | 610.62 |
溶解度 | ≥ 22.45mg/mL in DMSO | 储存条件 | Store at -20°C |
General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 1.6377 mL | 8.1884 mL | 16.3768 mL |
5 mM | 0.3275 mL | 1.6377 mL | 3.2754 mL |
10 mM | 0.1638 mL | 0.8188 mL | 1.6377 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
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工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。