86770-68-5Relevant academic research and scientific papers
Sialyltransferase Inhibitors Suppress Breast Cancer Metastasis
Fu, Chih-Wei,Tsai, Han-En,Chen, Wei-Sheng,Chang, Tzu-Ting,Chen, Chia-Ling,Hsiao, Pei-Wen,Li, Wen-Shan
supporting information, p. 527 - 542 (2021/01/13)
We report the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Inhibitor design entailed the functionalization of lithocholic acid at C(3) and at the cyclopentane ring side chain. Among the series, FCW34 and FCW66 were shown to inhibit MDA-MB-231 cell migration as effectively as ST3GALIII-gene knockdown did. FCW34 was shown to inhibit tumor growth, reduce angiogenesis, and delay cancer cell metastasis in animal models. Furthermore, FCW34 inhibited vessel development and suppressed angiogenic activity in transgenic zebrafish models. Our results provide clear evidence that FCW34-induced sialyltransferase inhibition reduces cancer cell metastasis by decreasing N-glycan sialylation, thus altering the regulation of talin/integrin/FAK/paxillin and integrin/NFκB signaling pathways.
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.
MERTK DEGRADERS AND USES THEREOF
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Paragraph 00674; 00677, (2020/01/31)
The present invention provides compounds, compositions thereof, and methods of using the same.
HETEROCYCLIC DERIVATIVES
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, (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.
THERAPEUTIC METHODS
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Page/Page column 97; 99; 149; 151, (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.
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.
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.
METHODS FOR TREATING HEPATITIS B INFECTIONS
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Page/Page column 165; 167; 219, (2019/04/09)
Certain embodiments of the invention provide a method for identifying a patient that has a higher likelihood of responding to an HBV antigen inhibitor, such a method comprising detecting a hepatitis B virus (HBV) infected patient's genotype at one or more of the IL28B/A associated SNPs described herein, wherein the relevant genotype(s) described herein are indicative of a patient that has a higher likelihood of responding to an HBV antigen inhibitor as compared to an HBV infected patient having different genotypes at these locations.
From the Promiscuous Asenapine to Potent Fluorescent Ligands Acting at a Series of Aminergic G-Protein-Coupled Receptors
Hounsou, Candide,Baehr, Corinne,Gasparik, Vincent,Alili, Doria,Belhocine, Abderazak,Rodriguez, Thiéric,Dupuis, Elodie,Roux, Thomas,Mann, André,Heissler, Denis,Pin, Jean-Philippe,Durroux, Thierry,Bonnet, Dominique,Hibert, Marcel
, p. 174 - 188 (2018/02/10)
Monoamine neurotransmitters such as serotonin, dopamine, histamine, and noradrenaline have important and varied physiological functions and similar chemical structures. Representing important pharmaceutical drug targets, the corresponding G-protein-couple
TARGETED COMPOSITIONS
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Page/Page column 85; 87; 137; 139, (2018/11/10)
The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
