Thiochrome Enhances Acetylcholine Affinity at Muscarinic M4 Receptors: Receptor Subtype Selectivity via Cooperativity Rather than Affinity

2004 ◽  
Vol 65 (1) ◽  
pp. 257-266 ◽  
Author(s):  
S. Lazareno ◽  
V. Doležal ◽  
A. Popham ◽  
N. J. M. Birdsall
Keyword(s):  
Receptor Subtype ◽  
Subtype Selectivity

Modulation of PPAR receptor subtype selectivity of the ligands: Aliphatic chain vs aromatic ring as a spacer between pharmacophore and the lipophilic moiety

2008 ◽  
Vol 18 (24) ◽  
pp. 6471-6475 ◽  
Author(s):  
Harikishore Pingali ◽  
Mukul Jain ◽  
Shailesh Shah ◽  
Pravin Patil ◽  
Pankaj Makadia ◽  
...  
Keyword(s):  
Aromatic Ring ◽  
Receptor Subtype ◽  
Aliphatic Chain ◽  
Subtype Selectivity

scholarly journals GABAA Receptor Subtype Selectivity of the Proconvulsant Rodenticide TETS

2018 ◽  
Vol 114 (3) ◽  
pp. 310a-311a
Author(s):  
Brandon Pressly ◽  
Hai Minh Nguyen ◽  
Heike Wulff
Keyword(s):  
Gabaa Receptor ◽  
Receptor Subtype ◽  
Subtype Selectivity

Conformational Constraint of the Glycerol Moiety of Lysophosphatidylserine Affords Compounds with Receptor Subtype Selectivity

2016 ◽  
Vol 59 (8) ◽  
pp. 3750-3776 ◽  
Author(s):  
Sejin Jung ◽  
Asuka Inoue ◽  
Sho Nakamura ◽  
Takayuki Kishi ◽  
Akiharu Uwamizu ◽  
...  
Keyword(s):  
Receptor Subtype ◽  
Glycerol Moiety ◽  
Subtype Selectivity ◽  
Conformational Constraint

scholarly journals Optimisation of estrogen receptor subtype-selectivity of a 4-Aryl-4H-chromene scaffold previously identified by virtual screening

2020 ◽  
Vol 28 (5) ◽  
pp. 115261 ◽  
Author(s):  
Miriam Carr ◽  
Andrew J.S. Knox ◽  
Daniel K. Nevin ◽  
Niamh O'Boyle ◽  
Shu Wang ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Virtual Screening ◽  
Receptor Subtype ◽  
Subtype Selectivity

scholarly journals Structure and allosteric activity of a single-disulfide conopeptide from Conus zonatus at human α3β4 and α7 nicotinic acetylcholine receptors

2020 ◽  
Vol 295 (20) ◽  
pp. 7096-7112
Author(s):  
Madhan Kumar Mohan ◽  
Nikita Abraham ◽  
Rajesh R P ◽  
Benjamin Franklin Jayaseelan ◽  
Lotten Ragnarsson ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Therapeutic Potential ◽  
Receptor Site ◽  
Peptide Bond ◽  
Rational Drug Design ◽  
Receptor Subtype ◽  
Design Strategies ◽  
New Paradigm ◽  
Nicotinic Acetylcholine ◽  
Subtype Selectivity

Conopeptides are neurotoxic peptides in the venom of marine cone snails and have broad therapeutic potential for managing pain and other conditions. Here, we identified the single-disulfide peptides Czon1107 and Cca1669 from the venoms of Conus zonatus and Conus caracteristicus, respectively. We observed that Czon1107 strongly inhibits the human α3β4 (IC50 15.7 ± 3.0 μm) and α7 (IC50 77.1 ± 0.05 μm) nicotinic acetylcholine receptor (nAChR) subtypes, but the activity of Cca1669 remains to be identified. Czon1107 acted at a site distinct from the orthosteric receptor site. Solution NMR experiments revealed that Czon1107 exists in equilibrium between conformational states that are the result of a key Ser4–Pro5cis-trans isomerization. Moreover, we found that the X-Pro amide bonds in the inter-cysteine loop are rigidly constrained to cis conformations. Structure-activity experiments of Czon1107 and its variants at positions P5 and P7 revealed that the conformation around the X-Pro bonds (cis-trans) plays an important role in receptor subtype selectivity. The cis conformation at the Cys6–Pro7 peptide bond was essential for α3β4 nAChR subtype allosteric selectivity. In summary, we have identified a unique single-disulfide conopeptide with a noncompetitive, potentially allosteric inhibitory mechanism at the nAChRs. The small size and rigidity of the Czon1107 peptide could provide a scaffold for rational drug design strategies for allosteric nAChR modulation. This new paradigm in the “conotoxinomic” structure-function space provides an impetus to screen venom from other Conus species for similar, short bioactive peptides that allosterically modulate ligand-gated receptor function.

Sitaxentan for the Oral Treatment of Pulmonary Arterial Hypertension: Benefits from Endothelin Receptor Subtype Selectivity?

2009 ◽  
Vol 1 ◽  
pp. CMT.S2344
Author(s):  
Hermann A.M. Mucke
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Oral Treatment ◽  
Right Heart Failure ◽  
Oral Drug ◽  
Receptor Subtype ◽  
Endothelin Receptor ◽  
Good Tolerability ◽  
Subtype Selectivity ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a deadly and underdiagnosed disease which causes right heart failure secondary to pressure overload resulting from the thickening of the pulmonary artery endothelium, associated with elevated levels of circulating endothelin-1. Sitaxentan was the first endothelin antagonist with high selectivity for receptor subtype A (over subtype ET-B) to gain regulatory approval for the treatment of PAH in major pharmaceutical markets. This review traces the development history of sitaxentan, summarizes the designs and results from its clinical studies, and relates the drug's profile to that of the two other broadly available endothelin receptor antagonists, bosentan and ambrisentan. All three drugs have comparable therapeutic efficacy in the 6-minute walk test–-a frequently employed standard–-during the first 3-4 months of therapy. Their performance might differ slightly in other clinically relevant outcome measures, especially in longer-term treatment where fully comparable data have not yet been reported. In clinical trials of up to one year duration the propensity of sitaxentan to induce elevation of liver transaminases and hepatic failure was significantly lower than that of bosentan. As a once-daily oral drug with good tolerability sitaxentan has become a crucial element in the treatment of PAH.

Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern

2010 ◽  
Vol 20 (9) ◽  
pp. 2770-2775 ◽  
Author(s):  
Jos H.M. Lange ◽  
Martina A.W. van der Neut ◽  
Alice J.M. Borst ◽  
Mahmut Yildirim ◽  
Herman H. van Stuivenberg ◽  
...  
Keyword(s):  
Fine Tuning ◽  
Receptor Subtype ◽  
Cb2 Receptor ◽  
Substitution Pattern ◽  
Subtype Selectivity
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