Identification of CYP1A2 ligands by structure-based and ligand-based virtual screening

Vasanthanathan Poongavanam; Jeroen Lastdrager; Chris  Oostenbrink; Jan N M Commandeur; Nico P E Vermeulen; Flemming Steen Jørgensen; Lars Olsen

doi:10.1039/c1md00087j

Identification of CYP1A2 ligands by structure-based and ligand-based virtual screening

Vasanthanathan Poongavanam, Jeroen Lastdrager, Chris Oostenbrink, Jan N M Commandeur, Nico P E Vermeulen, Flemming Steen Jørgensen, Lars Olsen

6 Citationer (Scopus)

Abstract

The metabolic enzyme cytochrome P450 1A2 (CYP1A2) attracts much attention, not only because of its metabolism of drug compounds, but also due to its ability to convert procarcinogens to carcinogens. From a virtual screening, 41 compounds were selected and tested experimentally for inhibition of CYP1A2. Among these compounds, 16 inhibited the CYP1A2 activity by more than 50% at a concentration of 0.3 μM. The three most potent inhibitors have IC ₅₀ values of 20 nM. These inhibitors contain new scaffolds and may serve as starting points for further lead optimization. Thus, the applied virtual screening methods are useful for considering CYP1A2 inhibition, either to identify inhibitors of CYP1A2, e.g. for cancer therapy, or to identify undesirable inhibitory effects of the enzyme.

Originalsprog	Engelsk
Tidsskrift	MedChemComm
Vol/bind	2
Udgave nummer	9
Sider (fra-til)	853-859
ISSN	2040-2503
DOI	https://doi.org/10.1039/c1md00087j
Status	Udgivet - sep. 2011

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10.1039/c1md00087j

Citationsformater

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title = "Identification of CYP1A2 ligands by structure-based and ligand-based virtual screening",

abstract = "The metabolic enzyme cytochrome P450 1A2 (CYP1A2) attracts much attention, not only because of its metabolism of drug compounds, but also due to its ability to convert procarcinogens to carcinogens. From a virtual screening, 41 compounds were selected and tested experimentally for inhibition of CYP1A2. Among these compounds, 16 inhibited the CYP1A2 activity by more than 50% at a concentration of 0.3 μM. The three most potent inhibitors have IC 50 values of 20 nM. These inhibitors contain new scaffolds and may serve as starting points for further lead optimization. Thus, the applied virtual screening methods are useful for considering CYP1A2 inhibition, either to identify inhibitors of CYP1A2, e.g. for cancer therapy, or to identify undesirable inhibitory effects of the enzyme.",

keywords = "Former Faculty of Pharmaceutical Sciences",

author = "Vasanthanathan Poongavanam and Jeroen Lastdrager and Chris Oostenbrink and Commandeur, {Jan N M} and Vermeulen, {Nico P E} and J{\o}rgensen, {Flemming Steen} and Lars Olsen",

year = "2011",

month = sep,

doi = "10.1039/c1md00087j",

language = "English",

volume = "2",

pages = "853--859",

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T1 - Identification of CYP1A2 ligands by structure-based and ligand-based virtual screening

AU - Poongavanam, Vasanthanathan

AU - Lastdrager, Jeroen

AU - Oostenbrink, Chris

AU - Commandeur, Jan N M

AU - Vermeulen, Nico P E

AU - Jørgensen, Flemming Steen

AU - Olsen, Lars

PY - 2011/9

Y1 - 2011/9

N2 - The metabolic enzyme cytochrome P450 1A2 (CYP1A2) attracts much attention, not only because of its metabolism of drug compounds, but also due to its ability to convert procarcinogens to carcinogens. From a virtual screening, 41 compounds were selected and tested experimentally for inhibition of CYP1A2. Among these compounds, 16 inhibited the CYP1A2 activity by more than 50% at a concentration of 0.3 μM. The three most potent inhibitors have IC 50 values of 20 nM. These inhibitors contain new scaffolds and may serve as starting points for further lead optimization. Thus, the applied virtual screening methods are useful for considering CYP1A2 inhibition, either to identify inhibitors of CYP1A2, e.g. for cancer therapy, or to identify undesirable inhibitory effects of the enzyme.

AB - The metabolic enzyme cytochrome P450 1A2 (CYP1A2) attracts much attention, not only because of its metabolism of drug compounds, but also due to its ability to convert procarcinogens to carcinogens. From a virtual screening, 41 compounds were selected and tested experimentally for inhibition of CYP1A2. Among these compounds, 16 inhibited the CYP1A2 activity by more than 50% at a concentration of 0.3 μM. The three most potent inhibitors have IC 50 values of 20 nM. These inhibitors contain new scaffolds and may serve as starting points for further lead optimization. Thus, the applied virtual screening methods are useful for considering CYP1A2 inhibition, either to identify inhibitors of CYP1A2, e.g. for cancer therapy, or to identify undesirable inhibitory effects of the enzyme.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1039/c1md00087j

DO - 10.1039/c1md00087j

M3 - Journal article

SN - 2040-2503

VL - 2

SP - 853

EP - 859

JO - MedChemComm

JF - MedChemComm

IS - 9

ER -

Identification of CYP1A2 ligands by structure-based and ligand-based virtual screening

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