Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. / Bach, Anders; Stuhr-Hansen, Nicolai; Thorsen, Thor S; Bork, Nicolai; Moreira, Irina S; Frydenvang, Karla; Padrah, Shahrokh; Christensen, S Brøgger; Madsen, Kenneth L; Weinstein, Harel; Gether, Ulrik; Strømgaard, Kristian.

In: Organic & Biomolecular Chemistry, Vol. 8, No. 19, 2010, p. 4281-4288.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Bach, A, Stuhr-Hansen, N, Thorsen, TS, Bork, N, Moreira, IS, Frydenvang, K, Padrah, S, Christensen, SB, Madsen, KL, Weinstein, H, Gether, U & Strømgaard, K 2010, 'Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1', Organic & Biomolecular Chemistry, vol. 8, no. 19, pp. 4281-4288. https://doi.org/10.1039/c0ob00025f

APA

Bach, A., Stuhr-Hansen, N., Thorsen, T. S., Bork, N., Moreira, I. S., Frydenvang, K., Padrah, S., Christensen, S. B., Madsen, K. L., Weinstein, H., Gether, U., & Strømgaard, K. (2010). Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Organic & Biomolecular Chemistry, 8(19), 4281-4288. https://doi.org/10.1039/c0ob00025f

Vancouver

Bach A, Stuhr-Hansen N, Thorsen TS, Bork N, Moreira IS, Frydenvang K et al. Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. Organic & Biomolecular Chemistry. 2010;8(19):4281-4288. https://doi.org/10.1039/c0ob00025f

Author

Bach, Anders ; Stuhr-Hansen, Nicolai ; Thorsen, Thor S ; Bork, Nicolai ; Moreira, Irina S ; Frydenvang, Karla ; Padrah, Shahrokh ; Christensen, S Brøgger ; Madsen, Kenneth L ; Weinstein, Harel ; Gether, Ulrik ; Strømgaard, Kristian. / Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1. In: Organic & Biomolecular Chemistry. 2010 ; Vol. 8, No. 19. pp. 4281-4288.

Bibtex

@article{18611a90b0f411df825b000ea68e967b,
title = "Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1",
abstract = "Recently, we described the first small-molecule inhibitor, (E)-ethyl 2-cyano-3-(3,4-dichlorophenyl)acryloylcarbamate (1), of the PDZ domain of protein interacting with Calpha-kinase 1 (PICK1), a potential drug target against brain ischemia, pain and cocaine addiction. Herein, we explore structure-activity relationships of 1 by introducing subtle modifications of the acryloylcarbamate scaffold and variations of the substituents on this scaffold. The configuration around the double bond of 1 and analogues was settled by a combination of X-ray crystallography, NMR and density functional theory calculations. Thereby, docking studies were used to correlate biological affinities with structural considerations for ligand-protein interactions. The most potent analogue obtained in this study showed an improvement in affinity compared to 1 and is currently a lead in further studies of PICK1 inhibition.",
author = "Anders Bach and Nicolai Stuhr-Hansen and Thorsen, {Thor S} and Nicolai Bork and Moreira, {Irina S} and Karla Frydenvang and Shahrokh Padrah and Christensen, {S Br{\o}gger} and Madsen, {Kenneth L} and Harel Weinstein and Ulrik Gether and Kristian Str{\o}mgaard",
year = "2010",
doi = "10.1039/c0ob00025f",
language = "English",
volume = "8",
pages = "4281--4288",
journal = "Organic & Biomolecular Chemistry",
issn = "1470-4358",
publisher = "Royal Society of Chemistry",
number = "19",

}

RIS

TY - JOUR

T1 - Structure-activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1

AU - Bach, Anders

AU - Stuhr-Hansen, Nicolai

AU - Thorsen, Thor S

AU - Bork, Nicolai

AU - Moreira, Irina S

AU - Frydenvang, Karla

AU - Padrah, Shahrokh

AU - Christensen, S Brøgger

AU - Madsen, Kenneth L

AU - Weinstein, Harel

AU - Gether, Ulrik

AU - Strømgaard, Kristian

PY - 2010

Y1 - 2010

N2 - Recently, we described the first small-molecule inhibitor, (E)-ethyl 2-cyano-3-(3,4-dichlorophenyl)acryloylcarbamate (1), of the PDZ domain of protein interacting with Calpha-kinase 1 (PICK1), a potential drug target against brain ischemia, pain and cocaine addiction. Herein, we explore structure-activity relationships of 1 by introducing subtle modifications of the acryloylcarbamate scaffold and variations of the substituents on this scaffold. The configuration around the double bond of 1 and analogues was settled by a combination of X-ray crystallography, NMR and density functional theory calculations. Thereby, docking studies were used to correlate biological affinities with structural considerations for ligand-protein interactions. The most potent analogue obtained in this study showed an improvement in affinity compared to 1 and is currently a lead in further studies of PICK1 inhibition.

AB - Recently, we described the first small-molecule inhibitor, (E)-ethyl 2-cyano-3-(3,4-dichlorophenyl)acryloylcarbamate (1), of the PDZ domain of protein interacting with Calpha-kinase 1 (PICK1), a potential drug target against brain ischemia, pain and cocaine addiction. Herein, we explore structure-activity relationships of 1 by introducing subtle modifications of the acryloylcarbamate scaffold and variations of the substituents on this scaffold. The configuration around the double bond of 1 and analogues was settled by a combination of X-ray crystallography, NMR and density functional theory calculations. Thereby, docking studies were used to correlate biological affinities with structural considerations for ligand-protein interactions. The most potent analogue obtained in this study showed an improvement in affinity compared to 1 and is currently a lead in further studies of PICK1 inhibition.

U2 - 10.1039/c0ob00025f

DO - 10.1039/c0ob00025f

M3 - Journal article

C2 - 20668766

VL - 8

SP - 4281

EP - 4288

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

SN - 1470-4358

IS - 19

ER -

ID: 21593356