Resolution and in Vitro and Initial in Vivo Evaluation of Isomers of Iodine-125-Labeled 1-Azabicyclo[2.2.2]oct-3-yl .alpha.-Hydroxy-.alpha.-(1-iodo-1-propen-3-yl)-.alpha.-phenylacetate: A High-Affinity Ligand for the Muscarinic Receptor

1995 ◽  
Vol 38 (20) ◽  
pp. 3908-3917 ◽  
Author(s):  
Daniel W. McPherson ◽  
Carla R. Lambert ◽  
Kristi Jahn ◽  
Virendar Sood ◽  
Robert C. McRee ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
In Vivo Evaluation ◽  
High Affinity ◽  
Affinity Ligand ◽  
Iodine 125 ◽  
High Affinity Ligand

scholarly journals Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations

2019 ◽  
Author(s):  
Jihong Li ◽  
Yoshiyuki Fukase ◽  
Yi Shang ◽  
Wei Zou ◽  
José M. Muñoz-Félix ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Conformational Change ◽  
Small Molecule ◽  
High Affinity ◽  
Partial Agonists ◽  
Affinity Ligand ◽  
Human Therapy ◽  
High Affinity Ligand

AbstractThe integrin αVβ3 receptor has been implicated in several important diseases, but no αVβ3 antagonists are approved for human therapy. One possible limitation of current small-molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small-molecule pure antagonists TDI-4161 and TDI-3761. Both compounds inhibit αVβ3-mediated cell adhesion to αVβ3 ligands, but do not induce the conformational change as judged by antibody binding, electron microscopy, X-ray crystallography, and receptor priming studies. Both compounds demonstrated the favorable property of inhibiting bone resorptionin vitro, supporting potential value in treating osteoporosis. Neither, however, had the unfavorable property of the αVβ3 antagonist cilengitide of paradoxically enhancing aortic sprout angiogenesis at concentrations below its IC50, which correlates with cilengitide’s enhancement of tumor growthin vivo.Significance StatementαVβ3 is a potential therapeutic target for several important human diseases, but there are currently no αVβ3 antagonists approved for human therapy. Current candidates are primarily based on the Arg-Gly-Asp (RGD) motif and act as partial agonists in that they induce αVβ3 to undergo a conformational change that converts it into a high-affinity ligand-binding state. We have used structure-guided design to produce pure small-molecule αVβ3 antagonists that do not induce the conformational change as judged by protein crystallography, electron microscopy, and receptor priming. These compounds inhibit αVβ3-mediated bone resorptionin vitro, but unlike the partial agonist cilengitide, do not enhance angiogenesis at low doses, a property that correlates with low-dose cilengitide’s enhancement of tumor growthin vivo. These pure αVβ3 antagonists can help define αVβ3’s role in animal models. If they demonstrate benefits over partial agonists in these model systems, they may be appropriate to consider for human therapy.

In vitro and in vivo evaluation of new radiolabeled neurotensin(8–13) analogues with high affinity for NT1 receptors

2001 ◽  
Vol 28 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Elisa García-Garayoa ◽  
Lesley Allemann-Tannahill ◽  
Peter Bläuenstein ◽  
Martine Willmann ◽  
Nathalie Carrel-Rémy ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
High Affinity

scholarly journals In Vitro and In Vivo Evaluation of a 18F-Labeled High Affinity NOTA Conjugated Bombesin Antagonist as a PET Ligand for GRPR-Targeted Tumor Imaging

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81932 ◽  
Author(s):  
Zohreh Varasteh ◽  
Ola Åberg ◽  
Irina Velikyan ◽  
Gunnar Lindeberg ◽  
Jens Sörensen ◽  
...  
Keyword(s):  
Tumor Imaging ◽  
In Vivo Evaluation ◽  
High Affinity ◽  
Bombesin Antagonist

In vitro characterization of 6-[18F]fluoro-A-85380, a high-affinity ligand for α4β2* nicotinic acetylcholine receptors

Synapse ◽  
2004 ◽  
Vol 55 (2) ◽  
pp. 89-97 ◽  
Author(s):  
Daniela Gündisch ◽  
Andrei O. Koren ◽  
Andrew G. Horti ◽  
Olga A. Pavlova ◽  
Alane S. Kimes ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Nicotinic Acetylcholine ◽  
High Affinity ◽  
Affinity Ligand ◽  
In Vitro Characterization ◽  
High Affinity Ligand
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