PND-1186 (VS-4718)

Catalog No.S7653 Synonyms: SR-2156

PND-1186 (VS-4718) Chemical Structure

Molecular Weight(MW): 501.5

PND-1186 (VS-4718) is a reversible and selective FAK inhibitor with IC50 of 1.5 nM. Phase 1.

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Cited by 9 Publications

5 Customer Reviews

  • (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).

    Cell Death Differ, 2017, 24(5):889-902. PND-1186 (VS-4718) purchased from Selleck.

    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.

    Oncogene, 2017, 36(39):5522-5531. PND-1186 (VS-4718) purchased from Selleck.

  • 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 were then 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.

    Molecular and Cellular Biology, 2016, 36(10):1555-1568.. PND-1186 (VS-4718) purchased from Selleck.

    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.

    Toxicol Appl Pharmacol, 2018, 360:131-140. PND-1186 (VS-4718) purchased from Selleck.

  • Combined treatment of Dasatinib and PND‐1186 results in strong growth inhibition in HCC cell lines. A, Cell viability of HCC3‐4, HCC4‐4, SNU‐398, SNU‐475 cells when treated with Dasatinib, PND‐1186, or Dasatinib+PND‐1186 at ~IC50 concentration determined using crystal violet staining. Data are presented as mean ± SD; and P‐value was calculated using Mann‐Whitney U test. Each dot represents one treatment replicate. B, Expression of p‐Src, Src, p‐FAK and FAK in HCC cell lines analyzed using Western blotting. GAPDH was used as loading control. Das, Dasatinib; Veh, Vehicle

    Cancer Med, 2018, doi:10.1002/cam4.1777. PND-1186 (VS-4718) purchased from Selleck.

Purity & Quality Control

Choose Selective FAK Inhibitors

Biological Activity

Description PND-1186 (VS-4718) is a reversible and selective FAK inhibitor with IC50 of 1.5 nM. 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]

Assay
Methods Test Index PMID
Western blot
pY397 FAK / FAK / pY249 p130Cas / p130Cas / pY416 Src / Src ; 

PubMed: 20234191     


4T1 cells were seeded at 70% confluency on tissue culture plates coated with 10 µg/ml fibronectin. Cells were treated with vehicle (DMSO) or increasing PND-1186 addition for 1 h. Shown is total FAK, p130Cas, Src, or actin levels in cell lysates. Phospho-specific immunoblotting was performed in parallel for changes in FAK or Src activity (pY397 FAK or pY416 Src) and p130Cas tyrosine phosphorylation (pY249 p130Cas). 

β-catenin / Cyclin D1 / c-Myc ; 

PubMed: 25217697     


MM.1S and H929 cells were treated with VS-4718 (0, 2.5, 5, an 10 µM/L) for 24 hours. β-Catenin, c-Myc, and Cyclin D1 expression in these cells was inhibited by VS-4718.

20234191 25217697
Immunofluorescence
STAT3; 

PubMed: 30728047     


Immunofluorescence staining of STAT3 in MDA-MB 231 cells treated for 1 h with 100 nM E2 and 100 nM G1 alone or in combination with 1 μM FAK kinase inhibitor VS-4718. Cells were probed with rabbit anti-STAT3 primary antibody followed by FITC-conjugated secondary antibody in order to detect STAT3 displayed by the green signal, whereas the blue signal indicates the nuclei counterstained with DAPI. Images shown are representative of 10 random fields. 

30728047
Growth inhibition assay
Cell viability ; 

PubMed: 30425643     


Concentration-viability curves for parental and ABCG2- and ABCC1-overexpressing cells incubated with VS-4718. (A) Concentration-viability curves for NCI-H460 and NCI-H460/MX20 cells incubated with VS-4718 for 72 h. (B) Concentration-viability curves for S1 and S1-M1-80 cells incubated with VS-4718 for 72 h. (C)Concentration-viability curves for HEK293/pcDNA3.1 and HEK293/ABCG2 cells incubated with VS-4718 for 72 h. (D) Concentration-viability curves for KB-3-1 and KB-CV60 cells incubated with VS-4718 for 72 h. The cell viability was determined by MTT assay. Data are expressed as mean ±SD, representative of three independent experiments in triplicate.

30425643
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

Kinase Assay:

[1]

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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 Research:

[1]

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  • 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.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Mice bearing ID8 tumors or 4T1 tumors
  • Formulation: polyethylene glycol 400 (PEG400) in PBS (1:1) for s.c.; 5% sucrose for p.o.
  • Dosages: 100 mg/kg every 12 hours for s.c.; 0.5 mg/mL for p.o.
  • Administration: s.c. or p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 24 mg/mL (47.85 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.
5mg/mL

* 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.

Chemical Information

Molecular Weight 501.5
Formula

C25H26F3N5O3

CAS No. 1061353-68-1
Storage powder
in solvent
Synonyms SR-2156

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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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Frequently Asked Questions

  • Question 1:

    Whether the in vivo formulation of PND-1186 (VS-4718) using 2% DMSO+30% PEG 300+5% Tween 80+ddH2O is suitable for injection?

  • Answer:

    The formulation for PND-1186: 2% DMSO+30% PEG 300+5% Tween 80+ddH2O can generate a clear solution with highest contraction at 5mg/ml. It may be suitable for oral administration or injection.

FAK Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID