Publication

Structural Characterization of LRRK2 Inhibitors

Gilsbach, B. K., Messias, A. C., Ito, G., Sattler, M., Alessi, D. R., Wittinghofer, A. & Kortholt, A., 1-May-2015, In : Journal of Medicinal Chemistry. 58, 9, p. 3751−3756 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Gilsbach, B. K., Messias, A. C., Ito, G., Sattler, M., Alessi, D. R., Wittinghofer, A., & Kortholt, A. (2015). Structural Characterization of LRRK2 Inhibitors. Journal of Medicinal Chemistry, 58(9), 3751−3756. https://doi.org/10.1021/jm5018779

Author

Gilsbach, Bernd K ; Messias, Ana C ; Ito, Genta ; Sattler, Michael ; Alessi, Dario R ; Wittinghofer, Alfred ; Kortholt, Arjan. / Structural Characterization of LRRK2 Inhibitors. In: Journal of Medicinal Chemistry. 2015 ; Vol. 58, No. 9. pp. 3751−3756.

Harvard

Gilsbach, BK, Messias, AC, Ito, G, Sattler, M, Alessi, DR, Wittinghofer, A & Kortholt, A 2015, 'Structural Characterization of LRRK2 Inhibitors' Journal of Medicinal Chemistry, vol. 58, no. 9, pp. 3751−3756. https://doi.org/10.1021/jm5018779

Standard

Structural Characterization of LRRK2 Inhibitors. / Gilsbach, Bernd K; Messias, Ana C; Ito, Genta; Sattler, Michael; Alessi, Dario R; Wittinghofer, Alfred; Kortholt, Arjan.

In: Journal of Medicinal Chemistry, Vol. 58, No. 9, 01.05.2015, p. 3751−3756.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Gilsbach BK, Messias AC, Ito G, Sattler M, Alessi DR, Wittinghofer A et al. Structural Characterization of LRRK2 Inhibitors. Journal of Medicinal Chemistry. 2015 May 1;58(9):3751−3756. https://doi.org/10.1021/jm5018779


BibTeX

@article{5c2dfd0012854fd7a8196b338c56d5a8,
title = "Structural Characterization of LRRK2 Inhibitors",
abstract = "Kinase inhibition is considered to be an important therapeutic target for LRRK2 mediated Parkinson's disease (PD). Many LRRK2 kinase inhibitors have been reported but have yet to be optimized in order to qualify as drug candidates for the treatment of the disease. In order to start a structure-function analysis of such inhibitors, we mutated the active site of Dictyostelium Roco4 kinase to resemble LRRK2. Here, we show saturation transfer difference (STD) NMR and the first cocrystal structures of two potent in vitro inhibitors, LRRK2-IN-1 and compound 19, with mutated Roco4. Our data demonstrate that this system can serve as an excellent tool for the structural characterization and optimization of LRRK2 inhibitors using X-ray crystallography and NMR spectroscopy.",
author = "Gilsbach, {Bernd K} and Messias, {Ana C} and Genta Ito and Michael Sattler and Alessi, {Dario R} and Alfred Wittinghofer and Arjan Kortholt",
year = "2015",
month = "5",
day = "1",
doi = "10.1021/jm5018779",
language = "English",
volume = "58",
pages = "3751−3756",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "AMER CHEMICAL SOC",
number = "9",

}

RIS

TY - JOUR

T1 - Structural Characterization of LRRK2 Inhibitors

AU - Gilsbach, Bernd K

AU - Messias, Ana C

AU - Ito, Genta

AU - Sattler, Michael

AU - Alessi, Dario R

AU - Wittinghofer, Alfred

AU - Kortholt, Arjan

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Kinase inhibition is considered to be an important therapeutic target for LRRK2 mediated Parkinson's disease (PD). Many LRRK2 kinase inhibitors have been reported but have yet to be optimized in order to qualify as drug candidates for the treatment of the disease. In order to start a structure-function analysis of such inhibitors, we mutated the active site of Dictyostelium Roco4 kinase to resemble LRRK2. Here, we show saturation transfer difference (STD) NMR and the first cocrystal structures of two potent in vitro inhibitors, LRRK2-IN-1 and compound 19, with mutated Roco4. Our data demonstrate that this system can serve as an excellent tool for the structural characterization and optimization of LRRK2 inhibitors using X-ray crystallography and NMR spectroscopy.

AB - Kinase inhibition is considered to be an important therapeutic target for LRRK2 mediated Parkinson's disease (PD). Many LRRK2 kinase inhibitors have been reported but have yet to be optimized in order to qualify as drug candidates for the treatment of the disease. In order to start a structure-function analysis of such inhibitors, we mutated the active site of Dictyostelium Roco4 kinase to resemble LRRK2. Here, we show saturation transfer difference (STD) NMR and the first cocrystal structures of two potent in vitro inhibitors, LRRK2-IN-1 and compound 19, with mutated Roco4. Our data demonstrate that this system can serve as an excellent tool for the structural characterization and optimization of LRRK2 inhibitors using X-ray crystallography and NMR spectroscopy.

U2 - 10.1021/jm5018779

DO - 10.1021/jm5018779

M3 - Article

VL - 58

SP - 3751−3756

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 9

ER -

ID: 19579924