Related Experiment Video

Updated: Jun 14, 2025

In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues
10:36

In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues

Published on: March 21, 2017

7.6K

Synthesis and Anti-Cancer Activity of the Novel Selective Glucocorticoid Receptor Agonists of the Phenylethanolamine

Ekaterina M Zhidkova1, Leyla R Tilova2, Timur I Fetisov1

  • 1Department of Chemical Carcinogenesis, Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center for Oncology, Kashirskoe Shosse 24-15, Moscow 115478, Russia.

International Journal of Molecular Sciences
|August 29, 2024
PubMed

Insights

A new selective glucocorticoid receptor agonist (SEGRA), CpdA-03, shows promise for treating lymphoma. It effectively reduces tumor volume in mice with fewer side effects than current treatments.

Area of Science:

  • Pharmacology
  • Oncology
  • Medicinal Chemistry

Background:

  • Glucocorticoids (GCs) treat hematological malignancies but cause adverse effects.
  • GCs' effects stem from glucocorticoid receptor (GR) transrepression (anticancer) and transactivation (side effects).
  • Selective GR agonists (SEGRAs) target GR transrepression for better cancer therapy.

Purpose of the Study:

  • Develop novel SEGRAs with improved chemical stability and anticancer efficacy.
  • Evaluate CpdA-03, a novel SEGRA derivative, for its therapeutic potential in lymphoma.

Main Methods:

  • Synthesized CpdA derivatives (CpdA-01-CpdA-08) using two strategies.
  • Assessed GR affinity, stability, and SEGRA properties (TR without TA) of CpdA-03 in cell lines.
  • Evaluated CpdA-03's in vivo anti-lymphoma activity in a P388 murine model.

Main Results:

  • CpdA-03 demonstrated superior GR affinity and stability compared to CpdA.
  • CpdA-03 selectively induced GR transrepression (TR) without transactivation (TA) in lymphoma and leukemia cells.
  • In vivo, CpdA-03 reduced lymphoma tumor volume threefold, outperforming dexamethasone and CpdA.

Conclusions:

  • CpdA-03 is a novel, stable SEGRA with potent anti-lymphoma activity.
  • CpdA-03 exhibits selective GR modulation, suggesting a reduced side effect profile.
  • CpdA-03 represents a promising therapeutic candidate for lymphoma treatment.
Keywords:
CpdA-03anti-lymphoma activitymiceselective glucocorticoid receptor agoniststransactivationtransrepression

More Related Videos

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay05:17

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay

Published on: February 9, 2021

1.5K
An In Vitro Enzymatic Assay to Measure Transcription Inhibition by GalliumIII and H3 5,10,15-trispentafluorophenylcorroles09:00

An In Vitro Enzymatic Assay to Measure Transcription Inhibition by GalliumIII and H3 5,10,15-trispentafluorophenylcorroles

Published on: March 18, 2015

11.5K

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...
2.6K
Adrenergic Agonists: Direct-Acting Agents01:30

Adrenergic Agonists: Direct-Acting Agents

Drugs that mimic the action of endogenous catecholamines like noradrenaline and adrenaline are called adrenergic agonists or sympathomimetics. Based on their mechanism of action, sympathomimetics can be classified as direct-, indirect-, or mixed-acting sympathomimetics. Direct-acting adrenergic agonists activate adrenoceptors without affecting presynaptic neurons, making them independent of neuronal catecholamine-depleting agents like reserpine and guanethidine.
These agents can be classified...
1.4K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
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...
835
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
238
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
306