VS-4718   Click here for help

GtoPdb Ligand ID: 8742

Synonyms: PND-1186 | PND1186
Compound class: Synthetic organic
Comment: VS-4718 is an investigational, potent, reversible and orally active inhibitor of focal adhesion kinase (FAK; PTK2) [3]. FAK inhibitors are being investigated for their anti-cancer effects due to the association of increased FAK expression with tumor progression, and the links between integrins and FAK in the adhesion pathways [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 87.75
Molecular weight 501.2
XLogP 4.53
No. Lipinski's rules broken 0
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Canonical SMILES CNC(=O)c1ccccc1Nc1cc(ncc1C(F)(F)F)Nc1ccc(cc1OC)N1CCOCC1
Isomeric SMILES CNC(=O)c1ccccc1Nc1cc(ncc1C(F)(F)F)Nc1ccc(cc1OC)N1CCOCC1
InChI InChI=1S/C25H26F3N5O3/c1-29-24(34)17-5-3-4-6-19(17)31-21-14-23(30-15-18(21)25(26,27)28)32-20-8-7-16(13-22(20)35-2)33-9-11-36-12-10-33/h3-8,13-15H,9-12H2,1-2H3,(H,29,34)(H2,30,31,32)
No information available.
Summary of Clinical Use Click here for help
VS-4718 is being evaluated in Phase 1 clinical trials in patients with leukemias (NCT02215629) and with metastatic non-hematologic malignancies (NCT01849744).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
FAK inhibition disrupts the integrin signaling axis which controls anchorage-independent growth of ovarian cancer cells and induces cell-cycle arrest followed by cell death [2]. This effect is observed in other cancer cell types [3].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01849744 Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies Phase 1 Interventional Verastem, Inc.
NCT02215629 Dose Escalation Study in Acute Myeloid or B-Cell Acute Lymphoblastic Leukemia Phase 1 Interventional Verastem, Inc.