KPT-9274 - PAK 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEKPT-9274Cat. No.: HY-12793CAS No.: 1643913-93-2分式: CHFNO分量: 610.63作靶点: PAK; Nampt作通路: Cell Cycle/DNA Damage; Cytoskeleton; MetabolicEnzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 D

2、MSO : 32 mg/mL (52.40 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.6377 mL 8.1883 mL 16.3765 mL5 mM 0.3275 mL 1.6377 mL 3.2753 mL10 mM 0.1638 mL 0.8188 mL 1.6377 mL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，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 KPT-9274有服活性的 PAK4

3、/烟酰胺磷酸核糖 转移酶 (Nampt) 抑制剂，IC50 值分别为于 100 和 125nM。IC50 & Target PAK4 Nampt100 nM (IC50) 120 nM (IC50)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体外研究 KPT-9274 attenuates the PAK4/-catenin pathway, results in NAD depletion, and attenuates viability,invasion, and migration in several RCC cell lines

4、. Inhibition of NAMPT in a cell-free enzymatic assay usingrecombinant NAMPT shows an IC50 of approximately 120 nM for KPT-9274. KPT-9274 attenuates G2Mtransit and induces apoptosis in RCC cell lines 2.体内研究 KPT-9274 demonstrates a decrement of xenograft growth comparable with that of sunitinib. There

5、 areminimal KPT-9274 effects on the normal human RPTECs and no apparent toxicity in vivo. KPT-9274 iscurrently being investigated in a phase I human clinical trial of patients with advanced solid malignancies andNHL 2.PROTOCOLKinase Assay 2 For the effect of KPT-9274 on NAMPT activity, recombinant N

6、AMPT activity is measured using a coupled-enzyme reaction system. Briefly, NAMPT is incubated with KPT-9274, in the presence of ATP, nicotinamide,phosphoribosyl pyrophosphate (PRPP), and nicotinamide nucleotide adenylyltransferase 1 (NMNAT1), for 60minutes at 30C. Water-soluble tetrazolium salts (WS

7、T-1), alcohol dehydrogenase (ADH), diaphorase, andethanol are then added to each sample for 30 minutes. After the final incubation, the absorbance of thesamples is detected at 450 nm 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 RCC cel

8、l lines in addition to a normal primary renal primary proximal tubular epithelial cell line (RPTEC) areplated in 96-well plates (3,000 cells/well, n=8) and incubated for 72 hours with DMSO or KPT-9274 (0.1, 0.5,1, 2, 10 M). The cells are incubated in MTT solution/media mixture. Then, the MTT solutio

9、n is removed andthe blue crystalline precipitate in each well is dissolved in DMSO. Visible absorbance of each well at 540 nmis quantified using a microplate reader 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Male ath

10、ymic Nu/Nu mice (8 weeks of age and weight 25 g) are injected with 786-O (human RCC) cellssubcutaneously in the flank region. When tumor size reaches approximately 225 mm3, animals are randomlyassigned to treatment groups and treatments are started (day one). KPT-9274 drug product (30% KPT-9274API+4

11、0% polyvinylpyrrolidone K30+15% methyl cellulose+15% Phospholipon 90G) or vehicle (58%polyvinylpyrrolidone K30+21% methyl cellulose+21% Phospholipon 90G) is administered by oral gavagetwice daily for 5 days at 100 and 200 mg/kg twice a day. As a positive control, oral gavage of sunitinib invegetable

12、 oil is given. On day 28 of treatment, the mice are euthanized and the tumor volume is determined2MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. WO2015003166A12. Abu Aboud O, et al. Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth. Mol CancerTher. 2016 Sep;15(9):2119-29.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMcePdfHeightCaut