KPT 9274 (ATG-019)

Catalog No.S8444 Batch:S844403

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Technical Data

Formula

C35H29F3N4O3
Molecular Weight 610.62 CAS No. 1643913-93-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (163.76 mM)
Ethanol 100 mg/mL (163.76 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
2.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 50 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
PAK4 [1]
(Cell-free assay)		 NAMPT [1]
(Cell-free assay)
~120 nM
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].

Protocol (from reference)

Cell Assay:

[1]
  • Cell lines

    786-0, ACHN, Caki-1 and U-2 OS cells

  • Concentrations

    1μM and 5μM

  • Incubation Time

    12 hours

  • Method

    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).
Animal Study:

[1]
  • Animal Models

    786-O (VHL-mut) human RCC xenograft model (nude mice)

  • Dosages

    100 and 200 mg/kg

  • Administration

    by oral gavage

Selleck's KPT 9274 (ATG-019) has been cited by 7 publications

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(1):83-97] PubMed: 35121889
Targeting PAK4 to reprogram the vascular microenvironment and improve CAR-T immunotherapy for glioblastoma [ NAT CANCER, 2021, 2, 83–97] PubMed: None

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SHIPPING AND STORAGE
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