Home Angiogenesis FAK inhibitor - Apoptosis related activator PND-1186 (VS-4718)

PND-1186 (VS-4718)

Catalog No.S7653 Synonyms: SR-2156

For research use only.

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.

PND-1186 (VS-4718) Chemical Structure

CAS No. 1061353-68-1

Selleck's PND-1186 (VS-4718) has been cited by 28 publications

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FAK Signaling Pathways

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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 ; β-catenin / Cyclin D1 / c-Myc 20234191 25217697
Immunofluorescence STAT3 30728047
Growth inhibition assay Cell viability 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 (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 Research:

[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 Research:

[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.

Solubility (25°C)

In vitro

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

Chemical Information

Molecular Weight 501.5
Formula

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

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

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 μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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.

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