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Related Concept Videos

Adrenergic Agonists: Chemistry and Structure-Activity Relationship01:16

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of the aromatic...
Drug-Receptor Interaction: Agonist01:25

Drug-Receptor Interaction: Agonist

Agonists are drugs that interact with specific receptors in the body to produce a biological response. When an agonist binds to a receptor, it activates or enhances the receptor's function, leading to physiological effects. The interaction between agonist drugs and receptors is crucial for their therapeutic action in various medical treatments.
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship01:22

Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship

Cholinergic agonists or cholinomimetics mimic the action of acetylcholine to stimulate the parasympathetic nervous system. They are categorized into direct-acting and indirect-acting agents. The direct-acting cholinergic drugs induce the parasympathetic response by directly binding to the muscarinic or nicotine receptors. In comparison, the indirect-acting cholinergic drugs prevent acetylcholine hydrolysis, indirectly contributing to the extended parasympathetic response.
The direct-acting...
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers01:17

Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers

Adrenergic antagonists, or sympatholytics, inhibit adrenoceptor activation driven by catecholamines or agonists. Based on their adrenoceptor specificity, adrenergic blockers can be categorized into two primary groups: α-adrenergic blockers (α-blockers) and β-adrenergic blockers (β-blockers). α-blockers interact with α1 and α2 subtypes of α-adrenoceptors.
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...

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Related Experiment Video

Updated: Jul 14, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Design of a partial PPARdelta agonist.

Ingrid Pettersson1, Søren Ebdrup, Miroslav Havranek

  • 1Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. inpe@novonordisk.com

Bioorganic & Medicinal Chemistry Letters
|June 15, 2007
PubMed
Summary

Structure-based design yielded a partial agonist for the peroxisome proliferator-activated receptor delta (PPARdelta) by reducing maximum activation from 87% to 39%. This was confirmed by determining the crystal structure of the ligand-binding domain complex.

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Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
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Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography

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Last Updated: Jul 14, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography
09:09

Preparation and Delivery of Protein Microcrystals in Lipidic Cubic Phase for Serial Femtosecond Crystallography

Published on: September 20, 2016

Area of Science:

  • Medicinal Chemistry
  • Structural Biology
  • Molecular Pharmacology

Background:

  • Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear receptor involved in metabolic regulation.
  • Developing selective PPARdelta modulators is of therapeutic interest.
  • Partial agonists offer a potential therapeutic window by modulating receptor activity without full activation.

Purpose of the Study:

  • To design and characterize a partial agonist for the PPARdelta receptor using structure-based ligand design.
  • To investigate the molecular mechanisms underlying the reduced efficacy of the designed partial agonist.

Main Methods:

  • Structure-based drug design principles were applied to modify existing ligands.
  • Transactivation assays were performed to measure the functional activity of the designed compounds.
  • X-ray crystallography was employed to determine the complex structure of PPARdelta ligand-binding domain with the designed compound.

Main Results:

  • A novel compound was designed that functions as a partial agonist for PPARdelta.
  • The maximum transactivation activity of the designed compound was significantly reduced to 39% compared to the reference compound's 87%.
  • The crystal structure revealed specific interactions and conformational changes within the PPARdelta ligand-binding domain induced by the compound.

Conclusions:

  • Structure-based design is effective in generating partial agonists for PPARdelta.
  • Understanding the structural basis of reduced activation is crucial for further optimization of PPARdelta modulators.
  • The determined crystal structure provides valuable insights for the development of selective and efficacious PPARdelta-targeted therapeutics.