Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies

David E. Clark; Bohdan Waszkowycz; Melanie Wong; Peter M. Lockey; Robert Adalbert; Jonathan Gilley; Jonathan Clark; Michael P. Coleman

doi:10.1016/j.bmcl.2016.04.039

Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies

David E. Clark, Bohdan Waszkowycz, Melanie Wong, Peter M. Lockey, Robert Adalbert, Jonathan Gilley, Jonathan Clark, Michael P. Coleman

Cancer Research UK Manchester Institute

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

Abstract

NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration.

Original language	English
Pages (from-to)	2920-2926
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2016.04.039
Publication status	Published - 15 Jun 2016

Keywords

Axon degeneration
Molecular docking
NAMPT
Similarity searching
Virtual screening

Research Beacons, Institutes and Platforms

Manchester Cancer Research Centre

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2016.04.039Licence: CC BY

Cite this

Clark, D. E., Waszkowycz, B., Wong, M., Lockey, P. M., Adalbert, R., Gilley, J., Clark, J., & Coleman, M. P. (2016). Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies. Bioorganic and Medicinal Chemistry Letters, 26(12), 2920-2926. https://doi.org/10.1016/j.bmcl.2016.04.039

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abstract = "NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration.",

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author = "Clark, {David E.} and Bohdan Waszkowycz and Melanie Wong and Lockey, {Peter M.} and Robert Adalbert and Jonathan Gilley and Jonathan Clark and Coleman, {Michael P.}",

year = "2016",

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Clark, DE, Waszkowycz, B, Wong, M, Lockey, PM, Adalbert, R, Gilley, J, Clark, J & Coleman, MP 2016, 'Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies', Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 12, pp. 2920-2926. https://doi.org/10.1016/j.bmcl.2016.04.039

Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies. / Clark, David E.; Waszkowycz, Bohdan; Wong, Melanie et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 12, 15.06.2016, p. 2920-2926.

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

TY - JOUR

T1 - Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies

AU - Clark, David E.

AU - Waszkowycz, Bohdan

AU - Wong, Melanie

AU - Lockey, Peter M.

AU - Adalbert, Robert

AU - Gilley, Jonathan

AU - Clark, Jonathan

AU - Coleman, Michael P.

PY - 2016/6/15

Y1 - 2016/6/15

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AB - NAMPT may represent a novel target for drug discovery in various therapeutic areas, including oncology and inflammation. Additionally, recent work has suggested that targeting NAMPT has potential in treating axon degeneration. In this work, publicly available X-ray co-crystal structures of NAMPT and the structures of two known NAMPT inhibitors were used as the basis for a structure- and ligand-based virtual screening campaign. From this, two novel series of NAMPT inhibitors were identified, one of which showed a statistically significant protective effect when tested in a cellular model of axon degeneration.

KW - Axon degeneration

KW - Molecular docking

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KW - Similarity searching

KW - Virtual screening

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SN - 0960-894X

VL - 26

SP - 2920

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JO - Bioorganic and Medicinal Chemistry Letters

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ER -

Application of virtual screening to the discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) inhibitors with potential for the treatment of cancer and axonopathies

Abstract

Keywords

Research Beacons, Institutes and Platforms

UN SDGs

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