Label free fragment screening using surface plasmon resonance as a tool for fragment finding - analyzing parkin, a difficult CNS target.

Autor: Karin Regnström, Jiangli Yan, Lan Nguyen, Kari Callaway, Yanli Yang, Linnea Diep, Weimei Xing, Anirban Adhikari, Paul Beroza, Roy K Hom, Brigit Riley, Don Rudolph, Michael F Jobling, Jeanne Baker, Jennifer Johnston, Andrei Konradi, Michael P Bova, Dean R Artis

Publikováno v: PLoS ONE, Vol 8, Iss 7, p e66879 (2013)

Surface Plasmon Resonance (SPR) is rarely used as a primary High-throughput Screening (HTS) tool in fragment-based approaches. With SPR instruments becoming increasingly high-throughput it is now possible to use SPR as a primary tool for fragment fin

Externí odkaz: https://doaj.org/article/49e73ef974d742cb8de3fc7bf2fab6d1

Novel Small Molecules Targeting the Intrinsically Disordered Structural Ensemble of α-Synuclein Protect Against Diverse α-Synuclein Mediated Dysfunctions

Autor: Amandine Berthet, Daniel Schwizer, David A. Agard, Eliezer Masliah, Mariano C. Tabios, Thomas Neumann, Ted Yednock, Gergely Tóth, Stephen Ballaron, Brian Spencer, Lisa McConlogue, Nunilo Cremades, John P. Anderson, Hans-Dieter Junker, Jean-Christophe Rochet, Dale Schenk, Xiao-Hua Chen, John Christodoulou, Renate Sekul, Wenxian Mao, Michael F. Jobling, Carlos W. Bertoncini, Mitali A. Tambe, Inge Ott, Balazs G. Szoke, Shyra J. Gardai, Wherly P. Hoffman, Phuong Nguyen, Michael P. Bova, Jiahui Tao

Publikováno v: Scientific reports, vol 9, iss 1
Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019)
Zaguán: Repositorio Digital de la Universidad de Zaragoza
Universidad de Zaragoza
Zaguán. Repositorio Digital de la Universidad de Zaragoza
instname

The over-expression and aggregation of α-synuclein (αSyn) are linked to the onset and pathology of Parkinson’s disease. Native monomeric αSyn exists in an intrinsically disordered ensemble of interconverting conformations, which has made its the

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a51b2ff3cd4ab186a8300f90d79cdb8d
https://www.repository.cam.ac.uk/handle/1810/300238

Development of a Novel β-Secretase Binding Assay Using the AlphaScreen Platform

Autor: Michael F. Jobling, Donald Rudolph, Karin Regnstrom, Michael P. Bova, Danny Tam, Shendong Yuan, Ying-Zi Xu, David W. G. Wone, Dean R. Artis, Harry Cheung, Hing L. Sham, Zhao Ren, Xiaohua Chen

Publikováno v: SLAS Discovery. 18:695-704

Alzheimer's disease (AD) is a devastating neurodegenerative disease affecting millions of people. β-secretase-1 (BACE1), an enzyme involved in the processing of the amyloid precursor protein (APP) to form Aβ is a validated target for AD. Herein, th

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c411e985b4be97bfe6438dd1b4d1b05f
https://doi.org/10.1177/1087057113482138

Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch

Autor: Anna Liao, Gary Probst, Pamela S. Keim, Kang Hu, Roy K. Hom, David A. Quincy, Michael S. Dappen, Grace T. Kwong, Jenifer Smith, Martin L. Neitzel, Ying-zi Xu, Elizabeth F. Brigham, Kevin P. Quinn, Frédérique Bard, Minghua Sun, Jing Wu, John-Michael Sauer, Dora Kholodenko, Hongbin Zhang, William Wallace, Matthew N. Mattson, Patricia Sacayon, Jacek Jagodzinski, Hing L. Sham, Brian T. Peterson, Simeon Bowers, Jennifer Marugg, Guriqbal S. Basi, Lee H. Latimer, Susanna S. Hemphill, Darren B. Dressen, Karina Wong, Kevin Tanaka, Michael P. Bova, Pamela Santiago, Daniel K. Ness, Anh P. Truong, Wes Zmolek, Lany Ruslim, Christopher Willits, Michael K. Lee, Andrei W. Konradi, Xiaocong M. Ye, Lam Nguyen, Chris M. Semko, Ted A. Yednock, Ruth N. Motter, Albert W. Garofalo, Erich Goldbach, Pearl Tanaka, Danielle L. Aubele

Publikováno v: Journal of Medicinal Chemistry. 56:5261-5274

Herein, we describe our strategy to design metabolically stable γ-secretase inhibitors which are selective for inhibition of Aβ generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::c5b61686f688dd0abd9c5edac66d7201
https://doi.org/10.1021/jm301741t

Design, synthesis and structure–activity relationship of novel [3.3.1] bicyclic sulfonamide-pyrazoles as potent γ-secretase inhibitors

Autor: Chris M. Semko, Danielle L. Aubele, Guriqbal S. Basi, Wes Zmolek, Gary Probst, Matthew N. Mattson, Elizabeth F. Brigham, Erich Goldbach, Karina Wong, William A Wallace, John-Michael Sauer, Hing L. Sham, Lan K. Nguyen, Michael P. Bova, Andrei W. Konradi, Albert W. Garofalo, Susanna S. Hemphill, Darren B. Dressen, Kevin P. Quinn, Minghua Sun, Anh P. Truong, Simeon Bowers

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 21:5791-5794

The structure–activity relationship (SAR) of a novel, potent and metabolically stable series of sulfonamide-pyrazoles that attenuate β-amyloid peptide synthesis via γ-secretase inhibition is detailed herein. Sulfonamide-pyrazoles that are efficac

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c797a2f9e3d425d83f37dc2fbd3a6ac
https://doi.org/10.1016/j.bmcl.2011.08.008