139729-28-5Relevant academic research and scientific papers
TARGETED BIFUNCTIONAL DEGRADERS
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Page/Page column 189, (2021/04/17)
The present invention provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In another aspect, the present invention provides bifunctional compounds that can be used to promote or enhance degradation of certain autoantibodies. In certain embodiments, treatment or management of a disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein or the autoantibody in the subject. Thus, in certain embodiments, administration of a compound of the invention to the subject removes or reduces the circulation concentration of the circulating protein or the autoantibody, thus treating, ameliorating, or preventing the disease and/or disorder. In certain embodiments, the circulating protein is TNF.
Preparation method of AEEA
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Paragraph 0067-0069, (2021/10/27)
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of AEA. According to the preparation method of AEEA provided by the invention, amino on diglycol amine is protected by chloroacetyl chloride, then ring formation is carried out in the presence of NaH, and AEEA is obtained through hydrolysis. The method has the advantages of reduced reaction steps, low production cost, high product purity and few impurities, and is suitable for industrial large-scale production.
Optimization of IEDDA bioorthogonal system: Efficient process to improve trans-cyclooctene/tetrazine interaction
Béquignat, Jean-Baptiste,Boucheix, Claude,Canitrot, Damien,Chezal, Jean-Michel,Degoul, Fran?oise,Miot-Noirault, Elisabeth,Moreau, Emmanuel,Navarro-Teulon, Isabelle,Quintana, Mercedes,Rondon, Aurélie,Taiariol, Ludivine,Ty, Nancy
supporting information, (2020/07/21)
The antibody pretargeting approach for radioimmunotherapy (RIT) using inverse electron demand Diels-Alder cycloaddition (IEDDA) constitutes an emerging theranostic approach for solid cancers. However, IEDDA pretargeting has not reached clinical trial. The major limitation of the IEDDA strategy depends largely on trans-cyclooctene (TCO) stability. Indeed, TCO may isomerize into the more stable but unreactive cis-cyclooctene (CCO), leading to a drastic decrease of IEDDA efficiency. We have thus developed both efficient and reproducible synthetic pathways and analytical follow up for (PEGylated) TCO derivatives, providing high TCO isomeric purity for antibody modification. We have set up an original process to limit the isomerization of TCO to CCO before the mAbs’ functionalization to allow high TCO/tetrazine cycloaddition.
Preparation method of [2-[1-(Fmoc-amino)ethoxy]ethoxy]acetic acid
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Paragraph 0065; 0068; 0070, (2019/09/17)
The invention provides a preparation method of [2-[1-(Fmoc-amino)ethoxy]ethoxy]acetic acid. The preparation method comprises steps as follows: amino protection is performed on diglycolamine by use ofphthalic anhydride, an obtained intermediate and halo-acetic acid or halo-acetate are subjected to a reaction, deprotection or deprotection and hydrolysis are performed, a product reacts with a Fmoc-based amino protection reagent, and [2-[1-(Fmoc-amino)ethoxy]ethoxy]acetic acid is obtained. In the preparation method, phthalic anhydride and diglycolamine are taken as initial raw materials, short time is required by an amino protection reaction, an obtained intermediate compound has good stability, can be preserved for a long time and does not react with water, water-soluble impurities (such asthe raw material diglycolamine, a byproduct phthalic acid and the like) can be separated through extraction, so that an amino protection product with high purity is obtained, and the purity and the yield of the target product are also improved.
BIFUNCTIONAL SMALL MOLECULES TO TARGET THE SELECTIVE DEGRADATION OF CIRCULATING PROTEINS
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Page/Page column 72, (2019/11/04)
The present invention is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcyRI, FcRN, Transferrin or Macrophage Scavenger receptor. Pharmaceutical compositions based upon these bifunctional small molecules represent an additional aspect of the present invention. These compounds and/or compositions may be used to treat disease states and conditions by removing circulating proteins through degradation in the hepatocytes or macrophages of a patient or subject in need of therapy. Methods of treating disease states and/or conditions in which circulating proteins are associated with the disease state and/or condition are also described herein.
HDAC INHIBITORS-BASED ANTIBODY DRUG CONJUGATES (ADCs) AND USE IN THERAPY
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, (2018/10/25)
The present invention relates to novel Histone Deacetylase Inhibitors (HDACi)- based antibody drug conjugates particularly with antibodies directed to ErbB1, ErbB2 and ErbB3 receptors, pharmaceutical compositions comprising said antibodies as well as to their use in the treatment of cancer or tumor and other diseases where a modulation of one or more histone deacetylase isoforms can be effective for therapeutic interventions.
Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies
Yao, Hong,Wei, Guoxiang,Liu, Yanpeng,Yao, Hequan,Zhu, Zheying,Ye, Wencai,Wu, Xiaoming,Xu, Jinyi,Xu, Shengtao
, p. 1030 - 1034 (2018/10/15)
23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe 26c were performed in B16F10 cells, and the results suggested that probe 26c was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent.
Cell-targeted platinum nanoparticles and nanoparticle clusters
Papst, Stefanie,Brimble, Margaret A.,Evans, Clive W.,Verdon, Daniel J.,Feisst, Vaughan,Dunbar, P. Rod,Tilley, Richard D.,Williams, David E.
supporting information, p. 6567 - 6572 (2015/06/16)
Herein, we report the facile preparation of cell-targeted platinum nanoparticles (PtNPs), through the design of peptides that, as a single molecule added in small concentration during the synthesis, control the size of PtNP clusters during their growth, stabilise the PtNPs in aqueous suspension and enable the functionalisation of the PtNPs with a versatile range of cell-targeting ligands. Water-soluble PtNPs targeted respectively at blood group antigens and at integrin receptors are demonstrated.
An easy access to asymmetrically substituted oligoethylene glycols from 18-crown-6
Abronina, Polina I.,Zinin, Alexander I.,Orlova, Anna V.,Sedinkin, Sergey L.,Kononov, Leonid O.
, p. 4533 - 4535 (2013/08/23)
A new route for the preparation of multi-gram quantities of the heterobifunctional oligoethylene glycol (OEG) derivatives (n = 6, 7) is reported based on decyclization of 18-crown-6.
Semisynthesis of fluorescent metabolite sensors on cell surfaces
Brun, Matthias A.,Griss, Rudolf,Reymond, Luc,Tan, Kui-Thong,Piguet, Joachim,Peters, Ruud J.R.W.,Vogel, Horst,Johnsson, Kai
supporting information; experimental part, p. 16235 - 16242 (2011/12/01)
Progress in understanding signal transduction and metabolic pathways is hampered by a shortage of suitable sensors for tracking metabolites, second messengers, and neurotransmitters in living cells. Here we introduce a class of rationally designed semisyn
