Comparison of Three-Dimensional Ligand-based Pharmacophores among 11 Phosphodiesterases (PDE 1 to PDE 11) Pharmacophores

Sei Hwan Kim, Jiwon Choi, Kyungro Lee, Kyoung Tai No

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Phosphodiesterases (PDEs) are major regulators of cyclic nucleotide signaling with a variety of pharmacological functions. Currently, more than 30 drugs targeting PDEs are on the market, and many drug candidates are under development. In this study, we generated three-dimensional ligand-based pharmacophores (3D-LBPs) of PDE1 to PDE11 using the ligands of each PDE obtained from BindingDB to identify critical chemical features of novel potential PDE inhibitors and the accuracy of each model was evaluated by cost difference, test set prediction, and Fischer's randomization test. Among 10 generated pharmacophore hypotheses, Hypo1 was selected as the best hypothesis. Hypo1 hypothesis with the highest predictability of each PDE, have correlation coefficients larger than 0.9 and cost differences larger than 40. Since the generated pharmacophores were validated with four ways, cost analysis, Fischer randomization test, the test set prediction, and ligand profiling and got high predictability for all the 11 PDEs; the results in this study will be used to develop novel inhibitors of 11 PDEs that are highly selective for its subtypes.

Original languageEnglish
Pages (from-to)1033-1037
Number of pages5
JournalBulletin of the Korean Chemical Society
Volume38
Issue number9
DOIs
Publication statusPublished - 2017 Sep 1

Fingerprint

Phosphoric Diester Hydrolases
Ligands
Costs
Phosphodiesterase Inhibitors
Cyclic Nucleotides
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Cite this

@article{ef3866fe340c4ab39afb70bc08baa9cb,
title = "Comparison of Three-Dimensional Ligand-based Pharmacophores among 11 Phosphodiesterases (PDE 1 to PDE 11) Pharmacophores",
abstract = "Phosphodiesterases (PDEs) are major regulators of cyclic nucleotide signaling with a variety of pharmacological functions. Currently, more than 30 drugs targeting PDEs are on the market, and many drug candidates are under development. In this study, we generated three-dimensional ligand-based pharmacophores (3D-LBPs) of PDE1 to PDE11 using the ligands of each PDE obtained from BindingDB to identify critical chemical features of novel potential PDE inhibitors and the accuracy of each model was evaluated by cost difference, test set prediction, and Fischer's randomization test. Among 10 generated pharmacophore hypotheses, Hypo1 was selected as the best hypothesis. Hypo1 hypothesis with the highest predictability of each PDE, have correlation coefficients larger than 0.9 and cost differences larger than 40. Since the generated pharmacophores were validated with four ways, cost analysis, Fischer randomization test, the test set prediction, and ligand profiling and got high predictability for all the 11 PDEs; the results in this study will be used to develop novel inhibitors of 11 PDEs that are highly selective for its subtypes.",
author = "Kim, {Sei Hwan} and Jiwon Choi and Kyungro Lee and No, {Kyoung Tai}",
year = "2017",
month = "9",
day = "1",
doi = "10.1002/bkcs.11214",
language = "English",
volume = "38",
pages = "1033--1037",
journal = "Bulletin of the Korean Chemical Society",
issn = "0253-2964",
publisher = "Korean Chemical Society",
number = "9",

}

Comparison of Three-Dimensional Ligand-based Pharmacophores among 11 Phosphodiesterases (PDE 1 to PDE 11) Pharmacophores. / Kim, Sei Hwan; Choi, Jiwon; Lee, Kyungro; No, Kyoung Tai.

In: Bulletin of the Korean Chemical Society, Vol. 38, No. 9, 01.09.2017, p. 1033-1037.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparison of Three-Dimensional Ligand-based Pharmacophores among 11 Phosphodiesterases (PDE 1 to PDE 11) Pharmacophores

AU - Kim, Sei Hwan

AU - Choi, Jiwon

AU - Lee, Kyungro

AU - No, Kyoung Tai

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Phosphodiesterases (PDEs) are major regulators of cyclic nucleotide signaling with a variety of pharmacological functions. Currently, more than 30 drugs targeting PDEs are on the market, and many drug candidates are under development. In this study, we generated three-dimensional ligand-based pharmacophores (3D-LBPs) of PDE1 to PDE11 using the ligands of each PDE obtained from BindingDB to identify critical chemical features of novel potential PDE inhibitors and the accuracy of each model was evaluated by cost difference, test set prediction, and Fischer's randomization test. Among 10 generated pharmacophore hypotheses, Hypo1 was selected as the best hypothesis. Hypo1 hypothesis with the highest predictability of each PDE, have correlation coefficients larger than 0.9 and cost differences larger than 40. Since the generated pharmacophores were validated with four ways, cost analysis, Fischer randomization test, the test set prediction, and ligand profiling and got high predictability for all the 11 PDEs; the results in this study will be used to develop novel inhibitors of 11 PDEs that are highly selective for its subtypes.

AB - Phosphodiesterases (PDEs) are major regulators of cyclic nucleotide signaling with a variety of pharmacological functions. Currently, more than 30 drugs targeting PDEs are on the market, and many drug candidates are under development. In this study, we generated three-dimensional ligand-based pharmacophores (3D-LBPs) of PDE1 to PDE11 using the ligands of each PDE obtained from BindingDB to identify critical chemical features of novel potential PDE inhibitors and the accuracy of each model was evaluated by cost difference, test set prediction, and Fischer's randomization test. Among 10 generated pharmacophore hypotheses, Hypo1 was selected as the best hypothesis. Hypo1 hypothesis with the highest predictability of each PDE, have correlation coefficients larger than 0.9 and cost differences larger than 40. Since the generated pharmacophores were validated with four ways, cost analysis, Fischer randomization test, the test set prediction, and ligand profiling and got high predictability for all the 11 PDEs; the results in this study will be used to develop novel inhibitors of 11 PDEs that are highly selective for its subtypes.

UR - http://www.scopus.com/inward/record.url?scp=85029029881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029029881&partnerID=8YFLogxK

U2 - 10.1002/bkcs.11214

DO - 10.1002/bkcs.11214

M3 - Article

AN - SCOPUS:85029029881

VL - 38

SP - 1033

EP - 1037

JO - Bulletin of the Korean Chemical Society

JF - Bulletin of the Korean Chemical Society

SN - 0253-2964

IS - 9

ER -