Home Metabolism NAMPT inhibitor - PAK inhibitor KPT 9274 (ATG-019) For research use only.

KPT 9274 (ATG-019)

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.

KPT 9274 (ATG-019) Chemical Structure

KPT 9274 (ATG-019) Chemical Structure

CAS No. 1643913-93-2

Purity & Quality Control

KPT 9274 (ATG-019) Related Products

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
KB-8-5-11 qHTS assay P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen 31515284
KB-3-1 qHTS assay P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen 31515284
Click to View More Cell Line Experimental Data

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
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].
Cell Research 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).
In Vivo
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].
Animal Research Animal Models 786-O (VHL-mut) human RCC xenograft model (nude mice)
Dosages 100 and 200 mg/kg
Administration by oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02702492 Terminated
Solid Tumors|NHL
Karyopharm Therapeutics Inc
 June 2016 Phase 1

Chemical Information & Solubility

Molecular Weight 610.62 Formula

C35H29F3N4O3
CAS No. 1643913-93-2 SDF --
Smiles C1CN(CCC1(F)F)C(=O)C2=CC=C(C=C2)C3=CC(=C4C(=C3)C=C(O4)CNC(=O)C=CC5=CN=C(C=C5)N)C6=CC=C(C=C6)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (163.76 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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