Related Experiment Video

Updated: Jun 14, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

8.9K

Development of Tailless Homologue Receptor (TLX) Agonist Chemical Tools

Emily C Hank1, Minh Sai1, Till Kasch1

  • 1Department of Pharmacy, Ludwig-Maximilians-Universität (LMU) München, 81377 Munich, Germany.

Journal of Medicinal Chemistry
|September 5, 2024
PubMed

Insights

Researchers developed novel, potent TLX agonists to study neural stem cell regulation. These chemically diverse compounds are valuable tools for neurodegenerative disease research and target validation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Drug Discovery

Background:

  • The human tailless homologue receptor (TLX) is crucial for neural stem cell homeostasis.
  • TLX modulation holds therapeutic potential for neurodegenerative diseases.
  • A scarcity of TLX ligands hinders research and target validation.

Purpose of the Study:

  • To systematically optimize a TLX agonist scaffold.
  • To develop potent and selective TLX agonists for research applications.
  • To create chemically diverse agonists for target identification and validation.

Main Methods:

  • Fragment fusion approach for scaffold identification.
  • Systematic structural modifications and optimization.
  • In vitro assays to determine potency, binding affinity, selectivity, and toxicity.

Main Results:

  • Development of two novel TLX agonists with nanomolar potency and binding affinity.
  • Agonists demonstrated high selectivity and low toxicity, suitable for chemical tools.
  • The agonists possess distinct scaffolds, offering high chemical diversity.

Conclusions:

  • Novel TLX agonists have been successfully developed and optimized.
  • These agonists serve as valuable chemical probes for TLX research.
  • The developed agonists facilitate target identification and validation in neurodegenerative disease studies.

More Related Videos

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications09:39

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications

Published on: January 27, 2014

12.6K
Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

40.1K

Related Concept Videos

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...
2.4K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.4K
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...
903
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...
2.6K
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.7K
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...
679