A dock derived compound against laminin receptor (37 LR) exhibits anti-cancer properties in a prostate cancer cell line model

Oncotarget
Charles Samuel UmbaughMarxa L Figueiredo

Abstract

Laminin receptor (67 LR) is a 67 kDa protein derived from a 37 kDa precursor (37 LR). 37/67 LR is a strong clinical correlate for progression, aggression, and chemotherapeutic relapse of several cancers including breast, prostate, and colon. The ability of 37/67 LR to promote cancer cell aggressiveness is further increased by its ability to transduce physiochemical and mechanosensing signals in endothelial cells and modulate angiogenesis. Recently, it was demonstrated that 37/67 LR modulates the anti-angiogenic potential of the secreted glycoprotein pigment epithelium-derived factor (PEDF). Restoration of PEDF balance is a desirable therapeutic outcome, and we sought to identify a small molecule that could recapitulate known signaling properties of PEDF but without the additional complications of peptide formulation or gene delivery safety validation. We used an in silico drug discovery approach to target the interaction interface between PEDF and 37 LR. Following cell based counter screening and binding validation, we characterized a hit compound's anti-viability, activation of PEDF signaling-related genes, anti-wound healing, and anti-cancer signaling properties. This hit compound has potential for future development as a lea...Continue Reading

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Citations

Feb 13, 2020·International Journal of Molecular Sciences·Manoel Figueiredo NetoMarxa Leão Figueiredo
Oct 29, 2020·Journal of Biomolecular Structure & Dynamics·Hetal Damani ShahVinuthaa Murthy
Jul 3, 2021·Bioengineering·Marxa L FigueiredoTodd S Emrick
Apr 30, 2020·Molecular Therapy. Methods & Clinical Development·Marxa L FigueiredoTodd Emrick

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Methods Mentioned

BETA
nucleotide exchange
Assay
PCR
acetylation
transfection

Software Mentioned

AutodockTools
AutoDock Vina
pdbqt
Docking At TACC
Ingenuity Pathway Analysis ( IPA
Docking At UTMB
Perseus
Ingenuity Pathway Analysis Software
GraphPad Prism
Docking

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