A campaign targeting a conserved Hsp70 binding site uncovers how subcellular localization is linked to distinct biological activities

Autor: Hao Shao, Shuhei Taguwa, Luke Gilbert, Arielle Shkedi, Sara Sannino, Christopher J. Guerriero, Zachary J. Gale-Day, Zapporah T. Young, Jeffrey L. Brodsky, Jonathan Weissman, Jason E. Gestwicki, Judith Frydman

Publikováno v: Cell chemical biology. 29(8)

The potential of small molecules to localize within subcellular compartments is rarely explored. To probe this question, we measured the localization of Hsp70 inhibitors using fluorescence microscopy. We found that even closely related analogs had dr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d45ec1cf60ce50a889c13a138e8b8b17
https://pubmed.ncbi.nlm.nih.gov/35830852

Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells

Autor: Silvia Rinaldi, Victoria A. Assimon, Szu Yu Kuo, Giulia Morra, Giorgio Colombo, Hao Shao, Keith D. Green, Zapporah T. Young, Sylvie Garneau-Tsodikova, Isabelle R. Taylor, Xiaokai Li, Jason E. Gestwicki, Daniel Nguyen

Publikováno v: Chemical science (Camb. 2010. Print) 11 (2020): 1892–1904. doi:10.1039/c9sc04284a
info:cnr-pdr/source/autori:Taylor I.R.; Assimon V.A.; Kuo S.Y.; Rinaldi S.; Li X.; Young Z.T.; Morra G.; Green K.; Nguyen D.; Shao H.; Garneau-Tsodikova S.; Colombo G.; Gestwicki J.E./titolo:Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells/doi:10.1039%2Fc9sc04284a/rivista:Chemical science (Camb. 2010. Print)/anno:2020/pagina_da:1892/pagina_a:1904/intervallo_pagine:1892–1904/volume:11
Chemical science, vol 11, iss 7
Chemical Science

Understanding the selectivity of a small molecule for its target(s) in cells is an important goal in chemical biology and drug discovery. One powerful way to address this question is with dominant negative (DN) mutants, in which an active site residu

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57760f8b903fe9bfc56ae9186f307a38
https://publications.cnr.it/doc/437271

Exploration of Benzothiazole-Rhodacyanines as Allosteric Inhibitors of Protein-Protein Interactions with Heat Shock Protein 70 (Hsp70)

Autor: Len Neckers, Byron Hann, Michael A. Moses, Hao Shao, Sara N. Journey, Margarita Chernova, Luke A. Gilbert, Chakrapani Kalyanaraman, Xiaokai Li, Jonathan S. Weissman, Matthew P. Jacobson, Jason E. Gestwicki, Zapporah T. Young

Publikováno v: Journal of medicinal chemistry, vol 61, iss 14

Cancer cells rely on the chaperone, heat shock protein 70 (Hsp70), for survival and proliferation. Recently, benzothiazole-rhodacyanines have been shown to bind an allosteric site on Hsp70, interrupting its binding to nucleotide-exchange factors (NEF

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7705f87a9781f919dff9f7cbb34a8a62
https://europepmc.org/articles/PMC6104643/

Analogues of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, As Anti-Cancer Agents

Autor: Duxin Sun, Atta Ahmad, Xiaokai Li, Adam M. Kabza, Jamie N. Connarn, Jason E. Gestwicki, Erik R. P. Zuiderweg, Zapporah T. Young, Sharan R. Srinivasan

Publikováno v: ACS Medicinal Chemistry Letters. 4:1042-1047

The rhodacyanine, MKT-077, has antiproliferative activity against cancer cell lines through its ability to inhibit members of the heat shock protein 70 (Hsp70) family of molecular chaperones. However, MKT-077 is rapidly metabolized, which limits its

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::870a05f7c582afca7a136ac5a5a4cfd7
https://doi.org/10.1021/ml400204n

Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels

Autor: Umesh K. Jinwal, Xiaokai Li, Jason E. Gestwicki, Yoshinari Miyata, Sandlin P. Seguin, Chad A. Dickey, Sharan R. Srinivasan, Duxin Sun, Hsiu Fang Lee, Zapporah T. Young, Jeffrey L. Brodsky

Publikováno v: ACS chemical neuroscience, vol 4, iss 6

The molecular chaperone, heat shock protein 70 (Hsp70), is an emerging drug target for treating neurodegenerative tauopathies. We recently found that one promising Hsp70 inhibitor, MKT-077, reduces tau levels in cellular models. However, MKT-077 does

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b372f59871b8e4913b25a8fbb0cd70c2
https://escholarship.org/uc/item/3bf389sp