359629-73-5Relevant academic research and scientific papers
Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands
Bricelj, Ale?a,Dora Ng, Yuen Lam,Ferber, Dominic,Gütschow, Michael,Kr?nke, Jan,Kuchta, Robert,Müller, Sina,Monschke, Marius,Sosi?, Izidor,Steinebach, Christian,Wagner, Karl G.
supporting information, p. 1733 - 1738 (2021/11/16)
Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.
BIFUNCTIONAL AGENTS FOR PROTEIN RECRUITMENT AND/OR DEGRADATION
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Paragraph 0204; 0215; 0216-0217, (2021/06/26)
The disclosure relates to new compounds, including bifunctional compounds, to be used as modulators of ubiquitination for targeted protein degradation.
BIFUNCTIONAL COMPOUNDS AS CDK MODULATORS
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Paragraph 0228, (2020/02/16)
The present application provides compounds of formulae I and II that modulate CDK protein function. Methods of making the compounds, compositions containing the compounds, and the compounds for use in a method of treating or ameliorating of diseases, disorders, or conditions associated with CDK proteins, are also disclosed.
DEGRADERS OF WEE1 KINASE
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Paragraph 0124-0125, (2020/05/12)
Disclosed are bifunctional compounds (degraders) that target Wee1 tyrosine kinase for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat disease.
IRAK DEGRADERS AND USES THEREOF
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Paragraph 00962; 003372-003374, (2020/06/19)
The present invention provides compounds, compositions thereof, and methods of using the same.
IRAK DEGRADERS AND USES THEREOF
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Paragraph 00794; 001080-001082, (2021/01/23)
The present invention provides compounds, compositions thereof, and methods of using the same. The compounds include an IRAK binding moiety and a degradation inducing moiety (DIM). The DIM could be DTM a ligase binding moiety (LBM) or lysine mimetic. The compounds could be useful as IRAK protein kinase inhibitors and applied to IRAK mediated disorders.
Systematic Investigation of the Permeability of Androgen Receptor PROTACs
Scott, Duncan E.,Rooney, Timothy P. C.,Bayle, Elliott D.,Mirza, Tashfina,Willems, Henriette M. G.,Clarke, Jonathan H.,Andrews, Stephen P.,Skidmore, John
supporting information, p. 1539 - 1547 (2020/06/25)
Bifunctional molecules known as PROTACs simultaneously bind an E3 ligase and a protein of interest to direct ubiquitination and clearance of that protein, and they have emerged in the past decade as an exciting new paradigm in drug discovery. In order to investigate the permeability and properties of these large molecules, we synthesized two panels of PROTAC molecules, constructed from a range of protein-target ligands, linkers, and E3 ligase ligands. The androgen receptor, which is a well-studied protein in the PROTAC field was used as a model system. The physicochemical properties and permeability of PROTACs are discussed.
Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma
Hansen, Joshua D.,Correa, Matthew,Nagy, Mark A.,Alexander, Matt,Plantevin, Veronique,Grant, Virginia,Whitefield, Brandon,Huang, Dehua,Kercher, Timothy,Harris, Roy,Narla, Rama Krishna,Leisten, Jim,Tang, Yang,Moghaddam, Mehran,Ebinger, Katalin,Piccotti, Joseph,Havens, Courtney G.,Cathers, Brian,Carmichael, James,Daniel, Thomas,Vessey, Rupert,Hamann, Lawrence G.,Leftheris, Katerina,Mendy, Derek,Baculi, Frans,Lebrun, Laurie A.,Khambatta, Gody,Lopez-Girona, Antonia
, p. 6648 - 6676 (2020/09/11)
Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.
DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS
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Page/Page column 133, (2020/02/06)
Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.
ANTIPROLIFERATIVE COMPOUNDS AND SECOND ACTIVE AGENTS FOR COMBINED USE
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Paragraph 0265; 0269, (2020/07/23)
Provided herein are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof,
