206265-31-8Relevant 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.
HMG-COA REDUCTASE DEGRADATION INDUCING COMPOUND
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Paragraph 285; 301-304, (2021/10/11)
The present invention relates HMG-CoA reductase degradation inducing compounds. Specifically, the present invention relates a bifunctional compound in which a HMG-CoA reductase binding moiety and an E3 ubiquitin ligase-binding moiety are linked by a chemical linker. The present invention also relates a method for preparing the compounds, and a method for degradation of HMG-CoA reducatase using the compounds, as well as use for prevention or treatment of HMG-CoA reductase related diseases using the compounds.
BIVALENT TARGETED CONJUGATES
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, (2020/05/28)
The invention provides conjugates that comprise a bivalent targeting moiety, a nucleic acid, and optional linking groups as well as synthetic intermediates and synthetic methods useful for preparing the conjugates, compositions comprising the bidentate targeting ligands and the conjugates, as well as methods for targeting therapeutic nucleic acids with the bidentate conjugates. The conjugates are useful to target therapeutic nucleic acids.
THERAPEUTIC METHODS
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, (2020/05/28)
The invention provides methods and compositions for delivering a nucleic acid to a cell or the cytosol of the target cell. The method includes contacting the cell with, 1) a membrane-destabilizing polymer; and 2) a nucleic acid conjugate. The nucleic acid conjugate includes a targeting ligand bound to an optional linker and a nucleic acid.
HETEROCYCLIC DERIVATIVES
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Page/Page column 52; 100-101, (2020/08/13)
Compounds of the formula (I): Q1-Q2-Q3, in which Q1, Q2 and Q3 have the meanings indicated in Claim 1, degrade target proteins, and can be employed, inter alia, for the treatment of diseases such as cancer, multiple sclerosis, cardiovascular diseases, central nervous system injury and different forms of inflammation.
Atorvastatin Derived HMG-CoA Reductase Degradation Inducing Compound
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Paragraph 0196-0199, (2020/12/01)
The present invention relates to a HMG-CoA reductase degradation-inducing compound and, more specifically, to a bifunctional compound in which atorvastatin and E3 ubiquitin ligase binding moiety are chemically linked as HMG-CoA reductase binding moiety, to a production method thereof, to a HMG-CoA reductase degradation method using the same, and to a pharmaceutical composition for preventing or treating HMG-CoA reductase-related diseases, comprising the same.
IRAK DEGRADERS AND USES THEREOF
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, (2019/07/10)
The present invention provides compounds, compositions thereof, and methods of using the same.
Directed interactions of block copolypept(o) ides with mannose-binding receptors: Peptomicelles targeted to cells of the innate immune system
Heller, Philipp,Mohr, Nicole,Birke, Alexander,Weber, Benjamin,Reske-Kunz, Angelika,Bros, Matthias,Barz, Matthias
, p. 63 - 73 (2015/02/19)
Core-shell structures based on polypept(o)ides combine stealth-like properties of the corona material polysarcosine with adjustable functionalities of the polypeptidic core. Mannose-bearing block copolypept(o)ides (PSar-block-PGlu(OBn)) have been synthesized using 11-amino-3,6,9-trioxa-undecyl-2,3,4,6-tetra-O-acetyl-O-α-D-mannopyranoside as initiator in the sequential ring-opening polymerization of α-amino acid N-carboxyanhydrides. These amphiphilic block copolypept(o)ides self-assemble into multivalent PeptoMicelles and bind to mannose-binding receptors as expressed by dendritic cells. Mannosylated micelles showed enhanced cell uptake in DC 2.4 cells and in bone marrow-derived dendritic cells (BMDCs) and therefore appear to be a suitable platform for immune modulation.
6-Aminopenicillanic acid (6-APA) derivatives equipped with anchoring arms
Favre, Anna?ck,Grugier, Jér?me,Brans, Alain,Joris, Bernard,Marchand-Brynaert, Jacqueline
supporting information, p. 10818 - 10826 (2013/01/15)
6-APA derivatives were considered as selective labels for the construction of bifunctional linkers dedicated to the oriented immobilization of proteins on materials. Sulbactam-like compounds (i.e., 6-β-sulfonamido-penam sulfones) and penicillin G - like compounds (i.e., para-substituted 6-β- phenylacetamido-penams) were prepared and tested as irreversible inhibitors of representative β-lactamases and D,D-peptidases, respectively. The activity of the modified antibiotics was preserved despite their substitution with various anchoring arms. The (2-nitro-4,5-dimethoxy)-benzyl esters revealed of particular interest due to their capacity to acylate BlaR-CTD without deprotection.
A convenient route to diversely substituted icosahedral closomer nanoscaffolds
Jalisatgi, Satish S.,Kulkarni, Vikas S.,Tang, Betty,Houston, Zachary H.,Lee, Mark W.,Hawthorne, M. Frederick
supporting information; experimental part, p. 12382 - 12385 (2011/10/02)
The design and synthesis of icosahedral polyhedral borane closomer motifs based upon carbonate and carbamate anchoring groups for biomedical applications are described. Dodecacarbamate closomers containing easily accessible groups of interest at their linker termini were synthesized via activation of the B-OH vertices as aryl carbonates and their subsequent reaction with primary amines. Novel dodecacarbonate closomers were successfully synthesized for the first time by reacting [closo-B12(OH)12]2- with an excess of respective aryl chloroformates, utilizing relatively short reaction times, mild conditions and simple purification strategies, all of which had previously presented difficulties in closomer chemistry. This methodology for the 12-fold degenerate synthesis of carbonate and carbamate closomers will greatly facilitate further exploration of closomers as monodisperse nanomolecular delivery platforms.
