PND-1186 (VS-4718)

Name: PND-1186 (VS-4718)
Brand: Selleck Chemicals
SKU: S7653
Rating: 5 (18 reviews)

For research use only.

Catalog No.S7653 Synonyms: SR-2156

18 publications

CAS No. 1061353-68-1

PND-1186 (VS-4718, SR-2156) is a reversible and selective FAK inhibitor with IC50 of 1.5 nM. PND-1186 selectively promotes tumor cell apoptosis. Phase 1.

Selleck's PND-1186 (VS-4718) has been cited by 18 publications

Cell Stem Cell, 2018, 22(1):35-49

PubMed: 29249464 ( click the link to review the publication )

Cell Rep, 2020, 28;30(4):969-983e4

PubMed: 31956073 ( click the link to review the publication )

Oncogene, 2020, 39(20):4014-4027

PubMed: 32205868 ( click the link to review the publication )

J Cell Biol, 2020, 219(2)

PubMed: 31914171 ( click the link to review the publication )

Mol Cancer Ther, 2020, 19(2):637-649

PubMed: 31784455 ( click the link to review the publication )

J Invest Dermatol, 2020, S0022-202X(20)31981-3

PubMed: 32805217 ( click the link to review the publication )

Reprod Biol, 2020, 10.1016

PubMed: 32113856 ( click the link to review the publication )

Strahlenther Onkol, 2020, 10.1007/s00066-020-01666-0

PubMed: 32705304 ( click the link to review the publication )

Clin Cancer Res, 2019, 25(14):4552-4566

PubMed: 30979745 ( click the link to review the publication )

Nat Cell Biol, 2018, 20(10):1203-1214

PubMed: 30202050 ( click the link to review the publication )

J Cell Sci, 2018, 131(3)

PubMed: 29222114 ( click the link to review the publication )

Toxicol Appl Pharmacol, 2018, 360:131-140

PubMed: 30292832 ( click the link to review the publication )

Cancer Med, 2018, 10.1002/cam4.1777

PubMed: 30370649 ( click the link to review the publication )

Cell Death Differ, 2017, 10.1038/cdd.2017.34

PubMed: 28338656 ( click the link to review the publication )

Oncogene, 2017, 10.1038/onc.2017.147

PubMed: 28553954 ( click the link to review the publication )

Sci Signal, 2017, 10(497)

PubMed: 28928239 ( click the link to review the publication )

Cell Rep, 2016, 15(9):1893-900

PubMed: 27210750 ( click the link to review the publication )

Mol Cell Biol, 2016, 36(10):1555-68

PubMed: 26976639 ( click the link to review the publication )

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, SR-2156) 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]

Assay

Methods	Test Index	PMID
Western blot	pY397 FAK / FAK / pY249 p130Cas / p130Cas / pY416 Src / Src ; PubMed: 20234191 Cancer Biol Ther 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 Blood 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 J Exp Clin Cancer Res 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 Front Pharmacol 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]	- Collapse 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]	- Collapse 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]	- Collapse 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. (Only for Reference)

References

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 Download PND-1186 (VS-4718) SDF

Molecular Weight	501.5
Formula	C₂₅H₂₆F₃N₅O₃
CAS No.	1061353-68-1
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	SR-2156
Smiles	CNC(=O)C1=CC=CC=C1NC2=CC(=NC=C2C(F)(F)F)NC3=C(C=C(C=C3)N4CCOCC4)OC

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-09-01)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01849744	Terminated	Drug: VS-4718	Non Hematologic Cancers\|Metastatic Cancer	Verastem Inc.	June 2013	Phase 1
NCT02215629	Withdrawn	Drug: VS-4718	Relapsed or Refractory Acute Myeloid Leukemia\|Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia	Verastem Inc.		Phase 1

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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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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PND-1186 (VS-4718)