VS-4718 (PND-1186)

Catalog No.S7653 Batch:S765303

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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)
Ethanol 3 mg/mL (5.98 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 VS-4718 (PND-1186) is a reversible and selective FAK inhibitor with IC50 of 1.5 nM. PND-1186 selectively promotes tumor cell apoptosis. Phase 1.
Targets
FAK [1]
(Cell-free assay)
1.5 nM
In vitro In vitro, PND-1186 inhibits 4T1 breast carcinoma motility, promotes 4T1 apoptosis in suspended conditions, and decreases 4T1 soft agar colony number and size. [1] In HEY and OVCAR8 cells, VS-4718 promotes G0-G1 cell-cycle arrest followed by cell death. [2]
In vivo In mice bearing 4T1 tumors, PND-1186 (100 mg/kg s.c.) inhibits 4T1 subcutaneous tumor growth by induction of apoptosis. In mice bearing ID8 tumors, PND-1186 (0.5 mg/mL for p.o.) also causes ovarian carcinoma tumor growth inhibition. [1]

Protocol (from reference)

Kinase Assay:

[1]
  • In vitro kinase activity

    GST-FAK in vitro kinase activity is measured and compared 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 are determined with various concentrations of test compounds 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 spetrophotometric color 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 PND-1186 (final concentration for 0.6 mL). In separate experiments, PND-1186 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.

Customer Product Validation

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

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

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

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

Selleck's VS-4718 (PND-1186) has been cited by 39 publications

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
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [ Gut, 2023, gutjnl-2022-327927] PubMed: 36977556
FAK suppresses antigen processing and presentation to promote immune evasion in pancreatic cancer [ Gut, 2023, 1–2] PubMed: None
Stiff matrix induces exosome secretion to promote tumour growth [ Nat Cell Biol, 2023, 25(3):415-424] PubMed: 36797475
VE-Cadherin modulates β-catenin/TCF-4 to enhance Vasculogenic Mimicry [ Cell Death Dis, 2023, 14(2):135] PubMed: 36797281
Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors [ Mol Ther Oncolytics, 2023, 28:31-43] PubMed: 36619294
FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway [ Cell Death Dis, 2022, 13(7):589] PubMed: 35803916
TM4SF1 promotes esophageal squamous cell carcinoma metastasis by interacting with integrin α6 [ Cell Death Dis, 2022, 13(7):609] PubMed: 35835740
Low-dose X-ray irradiation combined with FAK inhibitors improves the immune microenvironment and confers sensitivity to radiotherapy in pancreatic cancer [ Biomed Pharmacother, 2022, 151:113114] PubMed: 35594704
Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells [ Int J Mol Sci, 2022, 23(2)833] PubMed: 35055018

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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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