Related Experiment Video

Updated: Apr 6, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.7K

Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma

M Emmy M Dolman1, Evon Poon2, Marli E Ebus3

  • 1Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. memdolman@gmail.com.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 24, 2015
PubMed
Abstract

Insights

The cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 shows promise for treating high-risk neuroblastoma. It effectively kills MYCN-amplified neuroblastoma cells and reduces tumor growth in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Neuroblastomas with MYCN amplification have poor prognoses, necessitating new treatments.
  • Targeting cyclin-dependent kinase 2 (CDK2) has shown potential for selectively killing these cancer cells.

Purpose of the Study:

  • To evaluate the efficacy of the CDK inhibitor AT7519 in preclinical models of MYCN-amplified neuroblastoma.
  • To assess AT7519's impact on tumor growth, survival, and target inhibition in vivo.

Main Methods:

  • Preclinical testing of AT7519 on MYCN-amplified and MYCN single copy neuroblastoma cell lines.
  • In vivo studies using neuroblastoma xenografts and transgenic mouse models.
  • Analysis of tumor growth inhibition, apoptosis induction, and target engagement (p-Rb, p-NPM).

Main Results:

  • AT7519 demonstrated greater potency against MYCN-amplified neuroblastoma cells compared to MYCN single copy cells (LC50 1.7 vs 8.1 µmol/L).
  • Significant tumor growth inhibition and apoptosis induction were observed in xenograft models.
  • Treatment of Th-MYCN mice led to improved survival and substantial tumor regression (86% reduction).
  • Drug efficacy correlated with intratumoral AT7519 concentration and inhibition of CDK2 targets.

Conclusions:

  • AT7519 is a potent inhibitor of MYCN-amplified neuroblastoma.
  • The drug shows significant preclinical efficacy, supporting its potential as a novel therapeutic for high-risk neuroblastoma.

More Related Videos

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells05:29

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells

Published on: March 28, 2021

3.3K
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis09:45

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Published on: March 31, 2015

11.9K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.8K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.4K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K