- An electrochemically controlled supramolecular zip tie based on host-guest chemistry of CB[8]
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Three molecular threads incorporating two viologen units attached by an oligo-ethylene glycol chain of variable length and an electron rich naphthalene moiety were prepared. The internal viologen unit is connected to the naphthalene by a rigid linker that
- Barriada, Jose L.,Domarco, Olaya,Franchi, Paola,García, Marcos D.,Lucarini, Marco,Neira, Iago,Peinador, Carlos
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supporting information
p. 5228 - 5233
(2020/07/23)
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- Design, Synthesis, and Pharmacological Characterization of Heterobivalent Ligands for the Putative 5-HT2A/mGlu2Receptor Complex
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We report the synthesis of the first series of heterobivalent ligands targeting the putative heteromeric 5-HT2A/mGlu2 receptor complex, based on the 5-HT2A antagonist MDL-100,907 and the mGlu2 ago-PAM JNJ-42491293. The functional properties of monovalent and heterobivalent ligands were characterized in 5-HT2A-, mGlu2/Gqo5-, 5-HT2A/mGlu2-, and 5-HT2A/mGlu2/Gqo5-expressing HEK293 cells using a Ca2+ imaging assay and a [3H]ketanserin binding assay. Pronounced functional crosstalk was observed between the two receptors in 5-HT2A/mGlu2 and 5-HT2A/mGlu2/Gqo5 cells. While the synthesized monovalent ligands retained the 5-HT2A antagonist and mGlu2 ago-PAM functionalities, the seven bivalent ligands inhibited 5-HT-induced responses in 5-HT2A/mGlu2 cells and both 5-HT- and Glu-induced responses in 5-HT2A/mGlu2/Gqo5 cells. However, no definitive correlation between the functional potency and spacer length of the ligands was observed, an observation substantiated by the binding affinities exhibited by the compounds in 5-HT2A, 5-HT2A/mGlu2, and 5-HT2A/mGlu2/Gqo5 cells. In conclusion, while functional crosstalk between 5-HT2A and mGlu2 was demonstrated, it remains unclear how these heterobivalent ligands interact with the putative receptor complex.
- Poulie, Christian B. M.,Liu, Na,Jensen, Anders A.,Bunch, Lennart
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p. 9928 - 9949
(2020/09/12)
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- BIS(2-HALOACETAMIDO)-COMPOUNDS FOR USE AS LINKING AGENTS AND RESULTANT PRODUCTS WHICH COMPRISE ANTIBODIES, HALF-ANTIBODIES AND ANTIBODY FRAGMENTS
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Bis(2-haloacetamido)- compounds for use as linkers to chemically cross-linking multiple thiol groups, and particularly, although not exclusively, the thiol groups of cysteine amino acids in peptide chains are described, along with their use as linking age
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Page/Page column 27; 37-38
(2021/01/23)
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- NOVEL DIHYDROPYRIDINONE AND DIHYDROPYRIMIDINONE COMPOUNDS AND THEIR USE
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The present invention is directed to novel compounds of Formula I; pharmaceutically acceptable salts or solvates thereof, and their use.
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Page/Page column 66; 67
(2017/12/27)
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- SMALL MOLECULE BASED ANTIBODY-RECRUITING COMPOUNDS FOR CANCER TREATMENT
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The present invention relates to chimeric (including bifunctional) compounds, compositions comprising those compounds and methods of treating cancer in a patient or subject, especially including metastatic cancer where cancer cells exhibit overexpression (heightened expression) of cell surface urokinase-type plasminogen activator receptor (urokinase receptor) compared to normal (non-cancerous) cells. The compounds bind to the urokinase-type plasminogen activator receptor (uPAR) on the surface of a cancer cell, including a metastatic cancer cell, and consequently recruit native antibodies of the patient or subject where the antibodies can selectively degrade and/or deactivate targeted cancer cells through antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) against a large number and variety of cancers, thus providing cancer cell death and an inhibition of growth, elaboration and/or metastasis of the cancer, including remission and cure of the patient's cancer.
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Page/Page column 56; 57
(2017/03/08)
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- Re-engineering the Immune Response to Metastatic Cancer: Antibody-Recruiting Small Molecules Targeting the Urokinase Receptor
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Developing selective strategies to treat metastatic cancers remains a significant challenge. Herein, we report the first antibody-recruiting small molecule (ARM) that is capable of recognizing the urokinase-type plasminogen activator receptor (uPAR), a uniquely overexpressed cancer cell-surface marker, and facilitating the immune-mediated destruction of cancer cells. A co-crystal structure of the ARM-U2/uPAR complex was obtained, representing the first crystal structure of uPAR complexed with a non-peptide ligand. Finally, we demonstrated that ARM-U2 substantially suppresses tumor growth in vivo with no evidence of weight loss, unlike the standard-of-care agent doxorubicin. This work underscores the promise of antibody-recruiting molecules as immunotherapeutics for treating cancer.
- Rullo, Anthony F.,Fitzgerald, Kelly J.,Muthusamy, Viswanathan,Liu, Min,Yuan, Cai,Huang, Mingdong,Kim, Minsup,Cho, Art E.,Spiegel, David A.
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supporting information
p. 3642 - 3646
(2016/03/23)
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- Efficient synthesis of Hsp90 inhibitor dimers as potential antitumor agents
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The PU-H58-dimers 13a-15b were efficiently synthesized and their biological properties were evaluated. The copper-catalyzed alkyne azide coupling was effective in simultaneously linking three components via a triazole formation to afford the target dimers
- Sekiguchi, Hironori,Muranaka, Kazuhiro,Osada, Akiko,Ichikawa, Satoshi,Matsuda, Akira
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experimental part
p. 5732 - 5737
(2010/09/11)
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- Macrocyclic receptor molecules with a pendant carboxylic acid group for the complexation of urea
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The synthesis of 5,5'-di-tert-butyl-3-(carboxymethyl)biphenyl crown ethers and several lariat ethers with pendant carboxylic acid groups, together with the determinations of the pKa values of these crown ether carboxylic acids, are described.In
- Aarts, Veronika M. L. J.,Grootenhuis, Peter D. J.,Reinhoudt, David N.,Czech, Anna,Czech, Bronislaw P.,Bartsch, Richard A.
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