KPT 9274 (ATG-019)

製品コードS8444 バッチS844402

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C35H29F3N4O3
分子量 610.62 CAS No. 1643913-93-2
Solubility (25°C)* 体外 DMSO 100 mg/mL (163.76 mM)
Ethanol 100 mg/mL (163.76 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 KPT 9274 ( ATG-019) is an orally bioavailable small molecule that is a non-competitive dual inhibitor of PAK4 and NAMPT. It shows an IC50 of ~120 nM for NAMPT in a cell-free enzymatic assay.
in vitro KPT-9274 interferences with PAK4 and NAD biosynthetic pathways results in reduction of G2/M transit as well as induction of apoptosis and decrease in cell invasion and migration in several human RCC cell lines. The inhibition of the PAK4 pathway by KPT-9274 attenuates nuclear β-catenin as well as the Wnt/β-catenin targets cyclin D1 and c-Myc[1].
in vivo KPT-9274 administration to a 786-O (VHL-mut) human RCC xenograft model leads to dose-dependent inhibition of tumor growth with no apparent toxicity[1]. It also shows remarkable anti-tumor activity in sub-cutaneous xenograft models of pancreatic ductal adenocarcinoma (PDAC) cell lines and cancer stem cells as a single agent. KPT-9274 possesses desirable PK properties and is well tolerated in mice with the absence of any signs of toxicity when 200 mg/kg daily is administered either intravenously or orally[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 786-0, ACHN, Caki-1 and U-2 OS cells
濃度 1μM and 5μM
反応時間 12 hours
実験の流れ

The in vitro cell migration and invasion assays were performed using transwell chambers. For the transwell migration assay, 1.5×104 cells were seeded on top of the polycarbonate filters, and 0.6 ml of growth medium with DMSO or KPT-9274 (1μM and 5μM) was added to both the upper and lower wells. After incubation for 12 hours, the filters were swabbed with a cotton swab, fixed with methanol, and then stained with Giemsa solution. For the in vitro invasion assay, filters were coated with Matrigel, and 2.5×104 cells were seeded onto the Matrigel and incubated for 20 hours. The cells attached to the lower surface of the filter were counted under a light microscope (10× magnification).
動物実験 動物モデル 786-O (VHL-mut) human RCC xenograft model (nude mice)
投薬量 100 and 200 mg/kg
投与方法 by oral gavage

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Genomic and transcriptomic profiling of peripheral T cell lymphoma reveals distinct molecular and microenvironment subtypes [ Cell Rep Med, 2024, 5(2):101416] PubMed: 38350451
Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer [ Sci Rep, 2023, 13(1):3334] PubMed: 36849518
M2 macrophages drive leukemic transformation by imposing resistance to phagocytosis and improving mitochondrial metabolism [ Sci Adv, 2023, 9(15):eadf8522] PubMed: 37058562
PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways [ Biochem Biophys Rep, 2023, 10.1016/j.bbrep.2023.101544] PubMed: 37720313
PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways [ Biochem Biophys Rep, 2023, 35:101544] PubMed: 37720313
Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma [ NAT CANCER, 2021, 2, 83–97] PubMed: None

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。