Related Experiment Video

Updated: Feb 9, 2026

The Extraction of Liver Glycogen Molecules for Glycogen Structure Determination
04:50

The Extraction of Liver Glycogen Molecules for Glycogen Structure Determination

Published on: February 8, 2022

6.6K

9-ING-41, a small-molecule glycogen synthase kinase-3 inhibitor, is active in neuroblastoma

Andrey V Ugolkov1,2, Gennadiy I Bondarenko2, Oleksii Dubrovskyi2

  • 1Department of Medicine, Developmental Therapeutic Program, Division of Hematology/Oncology.

Anti-Cancer Drugs
|May 31, 2018
PubMed

Insights

Glycogen synthase kinase-3β (GSK-3β) is a promising target for advanced neuroblastoma. Inhibiting GSK-3β with 9-ING-41 promotes cancer cell death and enhances chemotherapy effectiveness, suggesting its clinical utility.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pediatric Medicine

Background:

  • Advanced stage neuroblastoma is an aggressive pediatric cancer with poor prognosis.
  • Glycogen synthase kinase-3β (GSK-3β) presents a potential therapeutic target for neuroblastoma treatment.

Purpose of the Study:

  • To investigate the role of GSK-3β in neuroblastoma.
  • To evaluate the efficacy of GSK-3β inhibitors, particularly 9-ING-41, in neuroblastoma treatment.
  • To assess the combination therapy of 9-ING-41 with CPT-11 in preclinical models.

Main Methods:

  • Immunohistochemical staining to detect GSK-3β expression in neuroblastoma tissues.
  • In vitro studies using GSK-3 inhibitors (AR-A014418, TDZD-8, 9-ING-41) to assess neuroblastoma cell growth.
  • Analysis of apoptosis-related protein expression (XIAP) and cell apoptosis.
  • In vivo mouse xenograft models to evaluate the antitumor effects of 9-ING-41 and CPT-11 combination therapy.

Main Results:

  • Positive GSK-3β expression was found in 67% of neuroblastoma cases.
  • GSK-3 inhibitors, especially 9-ING-41, significantly suppressed neuroblastoma cell growth.
  • Inhibition of GSK-3 led to reduced XIAP expression and increased cancer cell apoptosis.
  • Combination therapy with 9-ING-41 and CPT-11 demonstrated superior antitumor activity compared to monotherapy in xenograft models.

Conclusions:

  • GSK-3β is a viable therapeutic target in advanced neuroblastoma.
  • The small-molecule inhibitor 9-ING-41 shows potent preclinical efficacy.
  • Combination therapy with 9-ING-41 and CPT-11 warrants clinical investigation for advanced neuroblastoma patients.

More Related Videos

Radiochemical Assessment of Glycogen Synthase Enzyme Activity in Animal Tissue02:30

Radiochemical Assessment of Glycogen Synthase Enzyme Activity in Animal Tissue

Published on: October 24, 2025

193
Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism07:59

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism

Published on: August 19, 2021

4.5K

Related Concept Videos

Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.5K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
ATP Synthase: Structure01:18

ATP Synthase: Structure

ATP synthase or ATPase is among the most conserved proteins found in bacteria, mammals, and plants. This enzyme can catalyze a forward reaction in response to the electrochemical gradient, producing ATP from ADP and inorganic phosphate. ATP synthase can also work in a reverse direction by hydrolyzing ATP and generating an electrochemical gradient. Different forms of ATP synthases have evolved special features to meet the specific demands of the cell. Based on their specific feature, ATP...
15.7K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
553
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
17.3K