VS-4718 (PND-1186)

Catalog No.S7653 Batch:S765304

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Technical Data

Formula

C25H26F3N5O3
Molecular Weight 501.5 CAS No. 1061353-68-1
Solubility (25°C)* In vitro DMSO 100 mg/mL (199.4 mM)
Water Insoluble
Ethanol Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 VS-4718 (PND-1186) is a reversible and selective FAK inhibitor with an IC50 of 1.5 nM, which selectively promotes tumour cell apoptosis. Phase 1.
Targets
FAK
(Cell-free assay)
1.5 nM
In vitro In vitro, VS-4718 (PND-1186) inhibits 4T1 breast carcinoma motility, promotes 4T1 apoptosis in suspended conditions, and decreases 4T1 soft agar colony number and size. This compound also promotes G0-G1 cell-cycle arrest followed by cell death in HEY and OVCAR8 cells.
In Vivo In mice bearing 4T1 tumours, VS-4718 (PND-1186) (100 mg/kg s.c.) inhibits subcutaneous tumour growth by induction of apoptosis. This compound (0.5 mg/mL for p.o.) also causes ovarian carcinoma tumour growth inhibition in mice bearing ID8 tumours.

Protocol (from reference)

Kinase Assay:

[1]
  • In vitro kinase activity

    VS-4718 (PND-1186) is evaluated by measuring GST-FAK in vitro kinase activity and comparing it to His-tagged FAK 411–686 using the K-LISA screening kit and poly(Glu:Tyr) (4:1) copolymer as a substrate immobilized on microtiter plates. IC50 values for this compound are determined with various concentrations in a buffer containing 50 µM ATP and 10 mM MnCl2, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate for 5 min at room temperature. Serial diluted compounds are tested in triplicate. Substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies with spectrophotometric colour quantitation. IC50 values are determined using the Hill-Slope Model. Kinase selectivity profiling is performed by using the KinaseProfiler service.
Cell Assay:

[1]
  • Cell Lines

    Murine ID8 ovarian carcinoma cells

  • Concentrations

    ~1 μM

  • Incubation Time

    6 days

  • Method

    For soft agar assays, 48-well plates are coated with a 1:4 mix of 2% agar (EM Science) in 0.2 mL growth media (bottom layer). 5×104 cells are plated per well (in triplicate) in a mixture of 0.3% agar in 0.2 mL growth media (top layer). After agar solidification, 0.2 mL growth media is added containing DMSO or VS-4718 (PND-1186) (final concentration for 0.6 mL). In separate experiments, this compound is added after 4 days. After 10 days, colonies are imaged in phase contrast, enumerated by counting 9 fields (3 fields per well), and total area determined using Image J. For all analyses, experimental points are performed in triplicate and repeated at least two times.
Animal Study:

[1]
  • Animal Models

    Mice bearing ID8 tumors or 4T1 tumors

  • Dosages

    100 mg/kg every 12 hours for s.c.; 0.5 mg/mL for p.o.

  • Administration

    s.c. or p.o.

References

  • https://pubmed.ncbi.nlm.nih.gov/20234191/
  • https://pubmed.ncbi.nlm.nih.gov/24899686/

Customer Product Validation

<p>(a) Percentage of apoptotic HepG2 and Huh7.5 cells after 48 h of treatment with DMSO (Vehicle), 0.5 μM or 1 μM PND 1186 measured by Annexin V and flow cytometry. Values are plotted as mean±SD (*P<0.05; **P<0.01; versus Vehicle, n =3). (b) Representative WB for p21 and caspase-3 in HepG2 and Huh7.5 cells after 48 h of treatment with DMSO (0), 0.5 μM or 1 μM PND 1186. β-tubulin is reported as a loading control (n=2). (c) Relative mRNA expression of EZH2 and NOTCH2 genes as measured by qRT-PCR in HepG2 and Huh7.5 cells after 48 h of treatment with DMSO (Vehicle), 0.5 μM or 1 μM PND 1186 (*P<0.05; **P<0.01; versus Vehicle, n =3).</p>

, , Cell Death Differ, 2017, 24(5):889-902

<p>Cells treated with different concentrations of VS-4718 for 24 h on 3D Matrigel culture were immunostained for cleaved caspase-3 and F-actin (d), and observed using confocal microscopy. Images are representative of cells treated with 10 μM VS-4718. Arrowheads (d) indicate cleaved caspase-3 activity. Data are presented as the means±s.d. of three independent experiments. The bar graphs show the average proportion of PI-positive spheroids. *P<0.01. Scale bar, 50 μm.</p>

, , Oncogene, 2017, 36(39):5522-5531

Cells were added equally to coverslips pretreated with fibronectin at 10 g/ml. Kinase inhibitors were then applied to these cells at the indicated concentrations. U0126 is a MAP kinase inhibitor, PND1186 is an FAK kinase inhibitor, saracatinib is an Src kinase inhibitor, and wortmannin is a PI3K inhibitor. Twenty-five minutes later, cells were pulsed with 2mM5-FUrd for 10 min. Cells werethen instantly fixed and stained with anti-BrdU antibody to visualize newly synthesized RNA in situ. Representative images are shown. (First column) 5-FUrd staining. Magnification, ×10. (Third column) 5-FUrd staining. Magnification, ×40. (Second and fourth columns) DAPI staining.

Data from [ , , Molecular and Cellular Biology, 2016, 36(10):1555-1568. ]

HIEC cells were treated with FAK inhibitor (1 μM VS-4718), or DMSO for 24 h, then exposed to 5 Gy of radiation and samples were taken 6 and 24 h later. Levels of FAK, p-FAK, and γH2AX were examined using western blotting and GAPDH was used as a loading control.

Data from [ , , Toxicol Appl Pharmacol, 2018, 360:131-140 ]

Sellecks VS-4718 (PND-1186) Has Been Cited by 46 Publications

Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2α and VE-cadherin activation in uveal melanoma [ Cell Death Differ, 2025, 10.1038/s41418-025-01469-9] PubMed: 40000790
Focal adhesion kinase plays an essential role in Th17 cell differentiation by stimulating NF-κB signaling [ Front Immunol, 2025, 16:1596802] PubMed: 41050684
Exosomal Galectin-3 promotes peritoneal metastases in gastric adenocarcinoma via microenvironment alterations [ iScience, 2025, 28(1):111564] PubMed: 39811647
The role of focal adhesion kinase in bladder cancer: translation from in vitro to ex vivo human urothelial carcinomas [ Radiol Oncol, 2025, 59(3):349-367] PubMed: 40959921
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer [ Nat Commun, 2024, 15(1):3741] PubMed: 38702301
Viral infection induces inflammatory signals that coordinate YAP regulation of dysplastic cells in lung alveoli [ J Clin Invest, 2024, 134(19)e176828] PubMed: 39352385
Notochord segmentation in zebrafish controlled by iterative mechanical signaling [ Dev Cell, 2024, S1534-5807(24)00238-7] PubMed: 38697108
Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway [ Cell Death Dis, 2024, 15(2):108] PubMed: 38302407
Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells [ J Transl Med, 2024, 22(1):800] PubMed: 39210440
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [ Gut, 2023, 1–2] 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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