Linking ATP and allosteric sites to achieve superadditive binding with bivalent EGFR kinase inhibitors

Autor: Florian Wittlinger, Blessing C. Ogboo, Ekaterina Shevchenko, Tahereh Damghani, Calvin D. Pham, Ilse K. Schaeffner, Brandon T. Oligny, Surbhi P. Chitnis, Tyler S. Beyett, Alexander Rasch, Brian Buckley, Daniel A. Urul, Tatiana Shaurova, Earl W. May, Erik M. Schaefer, Michael J. Eck, Pamela A. Hershberger, Antti Poso, Stefan A. Laufer, David E. Heppner

Publikováno v: Communications Chemistry, Vol 7, Iss 1, Pp 1-14 (2024)

Abstract Bivalent molecules consisting of groups connected through bridging linkers often exhibit strong target binding and unique biological effects. However, developing bivalent inhibitors with the desired activity is challenging due to the dual mo

Externí odkaz: https://doaj.org/article/4d98b317db4743c79540cdb1697614f4

Examining molecular factors of inactive versus active bivalent EGFR inhibitors: A missing link in fragment-based drug design

Autor: Florian Wittlinger, Blessing C. Ogboo, Calvin D. Pham, Ilse K. Schaeffner, Surbhi P. Chitnis, Tahereh Damghani, Tyler S. Beyett, Alexander Rasch, Brian Buckley, Daniel A. Urul, Tatiana Shaurova, Earl W. May, Erik M. Schaefer, Michael J. Eck, Pamela A. Hershberger, Stefan A. Laufer, David E. Heppner

The optimization of linkers that connect fragments within drug binding sites represents an impediment in fragment-based drug discovery (FBDD). To improve our understand of the molecular factors that enable effective fragment linking, we have produced

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3f963dd0ecbce0aeb30216c4895f60e0
https://doi.org/10.26434/chemrxiv-2023-cs3xn

Phosphorylation of the Pro-X-Thr-Pro site in phosphatase inhibitor-2 by cyclin-dependent protein kinase during M-phase of the cell cycle

Autor: Erik M. Schaefer, Weiping Wang, David L. Brautigan, Bjarki Stefansson, Mingguang Li

Publikováno v: Cellular Signalling. 18:1318-1326

Protein phosphorylation serves as a primary mechanism for triggering events during mitosis and depends on coordinated regulation of kinases and phosphatases. Protein Ser-Thr phosphatase-1 (PP1) activity is essential for the metaphase to anaphase tran

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30a19b5763b712dcd0fdce205b417297
https://doi.org/10.1016/j.cellsig.2005.10.020

Phosphorylation of Phosphoprotein Enriched in Astrocytes (PEA-15) Regulates Extracellular Signal-regulated Kinase-dependent Transcription and Cell Proliferation

Autor: Mark H. Ginsberg, Angela Glading, Fan-Li Chou, Erik M. Schaefer, Joseph S. Krueger

Publikováno v: Krueger, Joseph; Chou, Fan-Li; Glading, Angela; Schaefer, Erik; & Ginsberg, Mark H. (2005). Phosphorylation of phosphoprotein enriched in astrocytes (PEA-15) regulates extracellular signal-regulated kinase-dependent transcription and cell proliferation. Molecular Biology of the Cell, 16(8), 3552-3561. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/2481622c

Cell cycle progression is dependent on the nuclear localization and transcriptional effects of activated extracellular signal-regulated kinase (ERK)1 and ERK2 mitogen-activated protein (MAP) kinases (ERK1/2). Phosphoprotein enriched in astrocytes (PE

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d465000101bca24d65eb249009bb8e0
https://europepmc.org/articles/PMC1182297/

Reciprocal feedback regulation of insulin receptor and insulin receptor substrate tyrosine phosphorylation by phosphoinositide 3-kinase in primary adipocytes

Autor: Alastair W. Poole, Christopher Bell, Donyang Jiang, Richard M. Denton, Jeremy M. Tavaré, Ingeborg Hers, Erik M. Schaefer

Publikováno v: The Biochemical journal. 368(Pt 3)

Signalling by the insulin receptor substrate (IRS) proteins is critically dependent on the tyrosine phosphorylation of specific binding sites that recruit Src homology 2 (SH2)-domain-containing proteins, such as the p85 subunit of phosphoinositide 3-

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2310dd7f70cfc53abbd199293178cf3
https://pubmed.ncbi.nlm.nih.gov/12220227