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ChemMedChem, 2010
Bioorganic & Medicinal Chemistry Letters, 2018
eLife
Bruton’s tyrosine kinase (BTK) is targeted in the treatment of B-cell disorders including leukemias and lymphomas. Currently approved BTK inhibitors, including Ibrutinib, a first-in-class covalent inhibitor of BTK, bind directly to the kinase active site. While effective at blocking the catalytic activity of BTK, consequences of drug binding on the global conformation of full-length BTK are unknown. Here, we uncover a range of conformational effects in full-length BTK induced by a panel of active site inhibitors, including large-scale shifts in the conformational equilibria of the regulatory domains. Additionally, we find that a remote Ibrutinib resistance mutation, T316A in the BTK SH2 domain, drives spurious BTK activity by destabilizing the compact autoinhibitory conformation of full-length BTK, shifting the conformational ensemble away from the autoinhibited form. Future development of BTK inhibitors will need to consider long-range allosteric consequences of inhibitor binding, ...
Journal of Chemical Information and Modeling, 2011
Proceedings of the National Academy of Sciences of the United States of America, 2018
Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets. Despite this interest, fundamental questions remain regarding the parameters most critical for achieving potency and selectivity. Here we employ a series of biochemical and cellular techniques to investigate requirements for efficient knockdown of Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase essential for B cell maturation. Members of an 11-compound PROTAC library were investigated for their ability to form binary and ternary complexes with BTK and cereblon (CRBN, an E3 ligase component). Results were extended to me...
Acta Crystallographica Section D Biological Crystallography, 2000
Analytical Biochemistry, 2009
TheScientificWorldJournal, 2013
Journal of immunology (Baltimore, Md. : 1950), 2016
Dorothee Pielow, Jana Newiger and Yassir El Jamouhi (eds.), Teachers and Students: Reflections on Learning in Near and Middle Eastern Cultures. Collected Studies in Honour of Sebastian Günther, Leiden, Boston: Brill, 340-370., 2024
TARIH BILIMLERI ALANINDA ULUSLARARASI ÇALIŞMALAR, 2024
internationalconference.com.my
Studia Patristica XXIV, 1993
UCD School of Sociology, 2023
Summer Experience 2022
British Journal of Medicine and Medical Research, 2016
Σ. Μανδαλάκη και Γ. Ρεθεμιωτάκης (επιμ), Μινωικός κόσμος. Ταξίδι στις απαρχές της Ευρώπης, Αρχαιολογικό Μουσείο Ηρακλείου 2015, 13-62
Journal of Physics B: Atomic, Molecular and Optical Physics, 2008