Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening

Research output: Contribution to journalJournal articlepeer-review

Standard

Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. / Markt, Patrick; Petersen, Rasmus K; Flindt, Esben N; Kristiansen, Karsten; Kirchmair, Johannes; Spitzer, Gudrun; Distinto, Simona; Schuster, Daniela; Wolber, Gerhard; Laggner, Christian; Langer, Thierry.

In: Journal of Medicinal Chemistry, Vol. 51, No. 20, 2008, p. 6303-6317.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Markt, P, Petersen, RK, Flindt, EN, Kristiansen, K, Kirchmair, J, Spitzer, G, Distinto, S, Schuster, D, Wolber, G, Laggner, C & Langer, T 2008, 'Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening', Journal of Medicinal Chemistry, vol. 51, no. 20, pp. 6303-6317. https://doi.org/10.1021/jm800128k

APA

Markt, P., Petersen, R. K., Flindt, E. N., Kristiansen, K., Kirchmair, J., Spitzer, G., Distinto, S., Schuster, D., Wolber, G., Laggner, C., & Langer, T. (2008). Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. Journal of Medicinal Chemistry, 51(20), 6303-6317. https://doi.org/10.1021/jm800128k

Vancouver

Markt P, Petersen RK, Flindt EN, Kristiansen K, Kirchmair J, Spitzer G et al. Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. Journal of Medicinal Chemistry. 2008;51(20):6303-6317. https://doi.org/10.1021/jm800128k

Author

Markt, Patrick ; Petersen, Rasmus K ; Flindt, Esben N ; Kristiansen, Karsten ; Kirchmair, Johannes ; Spitzer, Gudrun ; Distinto, Simona ; Schuster, Daniela ; Wolber, Gerhard ; Laggner, Christian ; Langer, Thierry. / Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. In: Journal of Medicinal Chemistry. 2008 ; Vol. 51, No. 20. pp. 6303-6317.

Bibtex

@article{10320510f75411ddbf70000ea68e967b,
title = "Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening",
abstract = "Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow based on a combination of pharmacophore modeling with 3D shape and electrostatic similarity screening techniques to discover novel scaffolds for PPAR ligands. From the resulting 10 virtual screening hits, five tested positive in human PPAR ligand-binding domain (hPPAR-LBD) transactivation assays and showed affinities for PPAR in a competitive binding assay. Compounds 5, 7, and 8 were identified as PPAR-alpha agonists, whereas compounds 2 and 9 showed agonistic activity for hPPAR-gamma. Moreover, compound 9 was identified as a PPAR-delta antagonist. These results demonstrate that our virtual screening protocol is able to enrich novel scaffolds for PPAR ligands that could be useful for drug development in the area of atherosclerosis, dyslipidaemia, and type 2 diabetes.",
author = "Patrick Markt and Petersen, {Rasmus K} and Flindt, {Esben N} and Karsten Kristiansen and Johannes Kirchmair and Gudrun Spitzer and Simona Distinto and Daniela Schuster and Gerhard Wolber and Christian Laggner and Thierry Langer",
year = "2008",
doi = "10.1021/jm800128k",
language = "English",
volume = "51",
pages = "6303--6317",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "20",

}

RIS

TY - JOUR

T1 - Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening

AU - Markt, Patrick

AU - Petersen, Rasmus K

AU - Flindt, Esben N

AU - Kristiansen, Karsten

AU - Kirchmair, Johannes

AU - Spitzer, Gudrun

AU - Distinto, Simona

AU - Schuster, Daniela

AU - Wolber, Gerhard

AU - Laggner, Christian

AU - Langer, Thierry

PY - 2008

Y1 - 2008

N2 - Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow based on a combination of pharmacophore modeling with 3D shape and electrostatic similarity screening techniques to discover novel scaffolds for PPAR ligands. From the resulting 10 virtual screening hits, five tested positive in human PPAR ligand-binding domain (hPPAR-LBD) transactivation assays and showed affinities for PPAR in a competitive binding assay. Compounds 5, 7, and 8 were identified as PPAR-alpha agonists, whereas compounds 2 and 9 showed agonistic activity for hPPAR-gamma. Moreover, compound 9 was identified as a PPAR-delta antagonist. These results demonstrate that our virtual screening protocol is able to enrich novel scaffolds for PPAR ligands that could be useful for drug development in the area of atherosclerosis, dyslipidaemia, and type 2 diabetes.

AB - Peroxisome proliferator-activated receptors (PPARs) are important targets for drugs used in the treatment of atherosclerosis, dyslipidaemia, obesity, type 2 diabetes, and other diseases caused by abnormal regulation of the glucose and lipid metabolism. We applied a virtual screening workflow based on a combination of pharmacophore modeling with 3D shape and electrostatic similarity screening techniques to discover novel scaffolds for PPAR ligands. From the resulting 10 virtual screening hits, five tested positive in human PPAR ligand-binding domain (hPPAR-LBD) transactivation assays and showed affinities for PPAR in a competitive binding assay. Compounds 5, 7, and 8 were identified as PPAR-alpha agonists, whereas compounds 2 and 9 showed agonistic activity for hPPAR-gamma. Moreover, compound 9 was identified as a PPAR-delta antagonist. These results demonstrate that our virtual screening protocol is able to enrich novel scaffolds for PPAR ligands that could be useful for drug development in the area of atherosclerosis, dyslipidaemia, and type 2 diabetes.

U2 - 10.1021/jm800128k

DO - 10.1021/jm800128k

M3 - Journal article

C2 - 18821746

VL - 51

SP - 6303

EP - 6317

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 20

ER -

ID: 10243462