KPT 9274 (ATG-019)

Catalog No.S8444 Batch:S844401

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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
* <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.)

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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
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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