Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions

Matthew W. Parker; Craig W. Vander Kooi

doi:10.1016/j.ab.2014.02.017

Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions

Matthew W. Parker, Craig W. Vander Kooi

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.

Original language	English
Pages (from-to)	4-6
Number of pages	3
Journal	Analytical Biochemistry
Volume	453
Issue number	1
DOIs	https://doi.org/10.1016/j.ab.2014.02.017
State	Published - May 15 2014

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) grants R01GM094155 (C.W.V.K.) and T32HL072743 (M.W.P.).

Funding

This work was supported by National Institutes of Health (NIH) grants R01GM094155 (C.W.V.K.) and T32HL072743 (M.W.P.).

Funders	Funder number
National Institutes of Health (NIH)	R01GM094155
National Heart, Lung, and Blood Institute (NHLBI)	T32HL072743

Keywords

Assay
Inhibitor
Ligand
Neuropilin
Receptor
VEGF

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.ab.2014.02.017

Cite this

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title = "Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions",

abstract = "Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.",

keywords = "Assay, Inhibitor, Ligand, Neuropilin, Receptor, VEGF",

author = "Parker, {Matthew W.} and {Vander Kooi}, {Craig W.}",

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AU - Parker, Matthew W.

AU - Vander Kooi, Craig W.

N1 - Funding Information: This work was supported by National Institutes of Health (NIH) grants R01GM094155 (C.W.V.K.) and T32HL072743 (M.W.P.).

PY - 2014/5/15

Y1 - 2014/5/15

N2 - Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.

AB - Vascular endothelial growth factor-C (VEGF-C) is a secreted growth factor essential for lymphangiogenesis. VEGF-C functions in both physiological and pathological lymphangiogenesis, particularly in tumor metastasis, making it an attractive therapeutic target. Members of two families of cell surface receptors transduce VEGF-C signals: neuropilin-2 (Nrp2) and VEGF-receptor (VEGFR)-2/3. Nrp2 is a promising target for inhibition because it is highly expressed in lymphatic vessels. Here we describe a microplate-based assay for discovery of VEGF-C/Nrp2 inhibitors. We optimize this assay for use in screening an inhibitor library and identify three novel Nrp2/VEGF-C binding inhibitors from the National Institutes of Health (NIH) Clinical Collection small molecule library.

KW - Assay

KW - Inhibitor

KW - Ligand

KW - Neuropilin

KW - Receptor

KW - VEGF

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Microplate-based screening for small molecule inhibitors of neuropilin-2/vascular endothelial growth factor-C interactions

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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