scholarly journals High affinity rigidified AT2 receptor ligands with indane scaffolds

MedChemComm ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 2146-2160 ◽  
Author(s):  
Charlotta Wallinder ◽  
Christian Sköld ◽  
Sara Sundholm ◽  
Marie-Odile Guimond ◽  
Samir Yahiaoui ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Side Chain ◽  
At2 Receptor ◽  
Receptor Ligands ◽  
Receptor Agonists ◽  
High Affinity ◽  
Receptor Agonists And Antagonists

Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives.

Protective effects of the angiotensin II AT2 receptor agonist compound 21 in ischemic stroke: a nose-to-brain delivery approach

2018 ◽  
Vol 132 (5) ◽  
pp. 581-593 ◽  
Author(s):  
Douglas M. Bennion ◽  
Chad H. Jones ◽  
Alex N. Dang ◽  
Jacob Isenberg ◽  
Justin T. Graham ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Angiotensin Ii ◽  
Receptor Agonist ◽  
At2 Receptor ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Compound 21 ◽  
Neuroprotective Actions

Significant neuroprotective effects of angiotensin II type 2 (AT2) receptor (AT2 receptor) agonists in ischemic stroke have been previously demonstrated in multiple studies. However, the routes of agonist application used in these pre-clinical studies, direct intracerebroventricular (ICV) and systemic administration, are unsuitable for translation into humans; in the latter case because AT2 receptor agonists are blood–brain barrier (BBB) impermeable. To circumvent this problem, in the current study we utilized the nose-to-brain (N2B) route of administration to bypass the BBB and deliver the selective AT2 receptor agonist Compound 21 (C21) to naïve rats or rats that had undergone endothelin 1 (ET-1)-induced ischemic stroke. The results obtained from the present study indicated that C21 applied N2B entered the cerebral cortex and striatum within 30 min in amounts that are therapeutically relevant (8.4–9 nM), regardless of whether BBB was intact or disintegrated. C21 was first applied N2B at 1.5 h after stroke indeed provided neuroprotection, as evidenced by a highly significant, 57% reduction in cerebral infarct size and significant improvements in Bederson and Garcia neurological scores. N2B-administered C21 did not affect blood pressure or heart rate. Thus, these data provide proof-of-principle for the idea that N2B application of an AT2 receptor agonist can exert neuroprotective actions when administered following ischemic stroke. Since N2B delivery of other agents has been shown to be effective in certain human central nervous system diseases, the N2B application of AT2 receptor agonists may become a viable mode of delivering these neuroprotective agents for human ischemic stroke patients.

New high affinity H3 receptor agonists without a basic side chain

2005 ◽  
Vol 13 (23) ◽  
pp. 6309-6323 ◽  
Author(s):  
Ruengwit Kitbunnadaj ◽  
Marcel Hoffmann ◽  
Silvina A. Fratantoni ◽  
Gerold Bongers ◽  
Remko A. Bakker ◽  
...  
Keyword(s):  
Side Chain ◽  
Receptor Agonists ◽  
High Affinity ◽  
H3 Receptor

N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands

2020 ◽  
pp. 115859
Author(s):  
Johan Wannberg ◽  
Johan Gising ◽  
Jens Lindman ◽  
Jessica Salander ◽  
Hugo Gutiérrez-de-Terán ◽  
...  
Keyword(s):  
At2 Receptor ◽  
Receptor Ligands ◽  
High Affinity

Activation of intracellular angiotensin AT2 receptors induces rapid cell death in human uterine leiomyosarcoma cells

2015 ◽  
Vol 128 (9) ◽  
pp. 567-578 ◽  
Author(s):  
Yi Zhao ◽  
Ulf Lützen ◽  
Jürgen Fritsch ◽  
Maaz Zuhayra ◽  
Stefan Schütze ◽  
...  
Keyword(s):  
Cell Death ◽  
Receptor Agonist ◽  
Uterine Leiomyosarcoma ◽  
At2 Receptor ◽  
Cytotoxic Effects ◽  
High Affinity ◽  
Compound 21 ◽  
Angiotensin Type ◽  
At2 Receptors

The angiotensin type 2 (AT2) receptor is substantially over-expressed in quiescent human uterine leiomyosarcoma cells and displays high densities in mitochondria. The high-affinity, non-peptide AT2 receptor agonist, Compound 21 exerts profound cytotoxic effects in these cells.

scholarly journals Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews

2017 ◽  
Vol 34 ◽  
Author(s):  
ALEXANDER H. WARD ◽  
JOHN T. SIEGWART ◽  
MICHAEL R. FROST ◽  
THOMAS T. NORTON
Keyword(s):  
Receptor Agonist ◽  
Reference Group ◽  
Day Treatment ◽  
Intravitreal Injections ◽  
Axial Component ◽  
Tree Shrews ◽  
Receptor Agonists ◽  
Dopamine D2 ◽  
D4 Receptor ◽  
Receptor Agonists And Antagonists

AbstractWe examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n= 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.

scholarly journals Assembly of high-affinity insulin receptor agonists and antagonists from peptide building blocks

2003 ◽  
Vol 100 (8) ◽  
pp. 4435-4439 ◽  
Author(s):  
L. Schaffer ◽  
R. E. Brissette ◽  
J. C. Spetzler ◽  
R. C. Pillutla ◽  
S. Ostergaard ◽  
...  
Keyword(s):  
Insulin Receptor ◽  
Building Blocks ◽  
Receptor Agonists ◽  
High Affinity ◽  
Receptor Agonists And Antagonists
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