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Akademický článek

Activation of Liver AMPK with PF-06409577 Corrects NAFLD and Lowers Cholesterol in Rodent and Primate Preclinical Models

Publikováno v: EBioMedicine, Vol 31, Iss , Pp 122-132 (2018)

Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-A

Externí odkaz: https://doaj.org/article/3a6b1a8ecd964eee8550aafb2b27ef05

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Akademický článek

Chemoproteomic profiling reveals that cathepsin D off-target activity drives ocular toxicity of β-secretase inhibitors

Publikováno v: Nature Communications, Vol 7, Iss 1, Pp 1-14 (2016)

Several β-secretase (BACE) inhibitors exhibit unexplained ocular toxicity in preclinical studies. Here the authors generate a clickable photoaffinity probe to interrogate off-targets in cells and animals, and identify inhibition of cathepsin D as a

Externí odkaz: https://doaj.org/article/5dfe4a29e6af43a49ee6c24207abc513

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Akademický článek

Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain.

Autor: Nathanael G Lintner, Kim F McClure, Donna Petersen, Allyn T Londregan, David W Piotrowski, Liuqing Wei, Jun Xiao, Michael Bolt, Paula M Loria, Bruce Maguire, Kieran F Geoghegan, Austin Huang, Tim Rolph, Spiros Liras, Jennifer A Doudna, Robert G Dullea, Jamie H D Cate

Publikováno v: PLoS Biology, Vol 15, Iss 3, p e2001882 (2017)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating the levels of plasma low-density lipoprotein cholesterol (LDL-C). Here, we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ri

Externí odkaz: https://doaj.org/article/c8c20b848f9a4b7e848edcb19074a5c8

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Development of a high-throughput crystal structure-determination platform for JAK1 using a novel metal-chelator soaking system

Autor: Ravi G. Kurumbail, Eric Johnson, Nicole Caspers, Timothy A. Subashi, Michael L. Vazquez, Francis Rajamohan, Lise R. Hoth, Neelu Kaila, Kieran F. Geoghegan, Ciarán N. Cronin, Seungil Han

Publikováno v: Acta Crystallographica Section F Structural Biology Communications. 72:840-845

Crystals of phosphorylated JAK1 kinase domain were initially generated in complex with nucleotide (ADP) and magnesium. The tightly bound Mg2+-ADP at the ATP-binding site proved recalcitrant to ligand displacement. Addition of a molar excess of EDTA h

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f988d0314bd6b824e8075d2cd21fbb23
https://doi.org/10.1107/s2053230x16016356

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A tag-free collisionally induced fragmentation approach to detect drug-adducted proteins by mass spectrometry

Autor: Alfin D. N. Vaz, T. Eric Ballard, Upendra P. Dahal, Andrew J. Bessire, Kieran F. Geoghegan, Richard P. Schneider

Publikováno v: Rapid Communications in Mass Spectrometry. 29:2175-2183

Rationale The covalent modification of proteins by toxicants, new chemical entities or drug molecules, either by metabolic activation or the presence of inherently reactive functional groups, is commonly implicated in organ toxicity and idiosyncratic

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::d6eaa08ad6929f45155ff51c7f90177d
https://doi.org/10.1002/rcm.7375

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Rational Targeting of Active-Site Tyrosine Residues Using Sulfonyl Fluoride Probes

Autor: Shenping Liu, Lee R. Roberts, Erik C. Hett, Mihir D. Parikh, Ariamala Gopalsamy, Kieran F. Geoghegan, Ralph P. Robinson, Michael A. Tones, Lyn H. Jones, Robert E. Kyne, Hua Xu, Carol A. Menard, Arjun Narayanan

Publikováno v: ACS Chemical Biology. 10:1094-1098

This work describes the first rational targeting of tyrosine residues in a protein binding site by small-molecule covalent probes. Specific tyrosine residues in the active site of the mRNA-decapping scavenger enzyme DcpS were modified using reactive

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7ccf8d774527c711c78291b05503aba
https://doi.org/10.1021/cb5009475

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Direct photocapture of bromodomains using tropolone chemical probes

Autor: Erik C. Hett, Parag Sahasrabudhe, Mathew T. Pletcher, R. Aldrin Denny, Alexandria P. Taylor, Shenping Liu, Arindrajit Basak, Andrew C. Flick, Paul D. Bonin, Eugene Lvovich Piatnitski Chekler, Ingrid A. Stock, Lyn H. Jones, Shores C. Salter, Kieran F. Geoghegan

Publikováno v: MedChemComm. 6:1018-1023

Medicinal chemistry techniques, including structure-based molecular design, fragment replacement and synthetic library enablement, were used to create potent inhibitors of bromodomain and extraterminal domain (BET) and CREB bindingprotein bromodomain

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::d83b3c89758edc5d3dce8705cc3e96ab
https://doi.org/10.1039/c5md00070j

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Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain

Autor: David W. Piotrowski, Jennifer A. Doudna, Kim F. McClure, Spiros Liras, Michael W. Bolt, Bruce A. Maguire, Austin Huang, Robert Dullea, Donna N. Petersen, Jun Xiao, Tim Rolph, Liuqing Wei, Jamie H. D. Cate, Allyn T. Londregan, Kieran F. Geoghegan, Nathanael G. Lintner, Paula M. Loria

Publikováno v: PLoS biology, vol 15, iss 3
PLoS Biology
PLoS Biology, Vol 15, Iss 3, p e2001882 (2017)

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cce1f6bc26417b37506fac86c75c8950
https://escholarship.org/uc/item/3p3893k1

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