Related Experiment Video

Updated: Feb 24, 2026

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
06:29

Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells

Published on: July 30, 2020

3.5K

Characterization of a highly selective inhibitor of the Aurora kinases

Fleur M Ferguson1, Zainab M Doctor1, Apirat Chaikuad2

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

Bioorganic & Medicinal Chemistry Letters
|August 19, 2017
PubMed

Insights

Researchers discovered a selective inhibitor (PLK4) for Aurora kinases A, B, and C, crucial for cell division. This potent compound offers a valuable tool for studying these kinases in cancer research, unlike less specific existing drugs.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Aurora kinases are critical regulators of mitosis and cell cycle progression.
  • Aurora kinases are validated cancer targets, leading to the development of numerous inhibitors.
  • Existing Aurora kinase inhibitors often lack selectivity, limiting their utility as research tools.

Purpose of the Study:

  • To discover and characterize a highly selective inhibitor of Aurora kinases A, B, and C.
  • To provide a specific chemical probe for investigating Aurora kinase-mediated signaling pathways.
  • To elucidate the structural basis of selective Aurora kinase inhibition.

Main Methods:

  • High-throughput screening for Aurora kinase inhibitors.
  • Cellular activity assays to assess potency and selectivity.
  • X-ray crystallography to determine the co-crystal structure of Aurora A with the inhibitor.

Main Results:

  • Discovery of a novel, highly selective inhibitor targeting Aurora kinases A, B, and C (designated PLK4).
  • The inhibitor exhibits potent cellular activity with minimal off-target effects.
  • The X-ray co-crystal structure reveals key interactions governing ligand binding and selectivity for Aurora A.

Conclusions:

  • PLK4 represents a significant advancement in selective Aurora kinase inhibition.
  • This selective inhibitor serves as an invaluable tool for dissecting Aurora kinase functions in biological systems.
  • Structural insights from the co-crystal complex will aid in the design of future kinase inhibitors.
Keywords:
Aurora kinaseCancerMitosisPan-Aurora inhibitorSelective kinase inhibitor

More Related Videos

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.3K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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

11.9K

Related Concept Videos

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...
9.0K
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...
6.1K
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...
6.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.9K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.8K