Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Inhibition of Cdk Activity

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Structure and mechanism of inhibition of lysine demethylase 2A (KDM2A) by compound 183c.

Communications chemistry·2026

Same author

Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.

Journal of medicinal chemistry·2026

Same author

Accuracy and homogeneity of dictionary-based T2-mapping dedicated to single slice and multi-slice multi-echo turbo-spin echo imaging.

Magnetic resonance imaging·2026

Same author

The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity.

Nature communications·2026

Same author

Dual-Species Fermentation of a <i>Lycium barbarum</i>-<i>Polygonatum cyrtonema</i> Composite Jiaosu Enhanced Antioxidant Activity and Alleviated Alcohol-Induced Liver Injury in Mice.

Foods (Basel, Switzerland)·2026

Same author

The molecular glue CLEO4-88 inhibits the ACAA1 thiolase by induced binding to GID4.

Nature chemical biology·2026

Search research articles

Related Experiment Video

Updated: Jun 15, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Discovery of RP-1664: A First-in-Class Orally Bioavailable, Selective PLK4 Inhibitor.

Frédéric Vallée¹, Matias Casás-Selves¹, Monica Bubenik¹

¹Repare Therapeutics, Inc., 7210 Frederick-Banting, Ville St-Laurent, QC H4S 2A1, Canada.

Journal of Medicinal Chemistry

|May 16, 2025

Summary

This summary is machine-generated.

Researchers developed RP-1664, a potent Polo-like kinase 4 (PLK4) inhibitor, to treat cancers with TRIM37 gene amplification. This drug candidate shows improved properties and is now in Phase 1 clinical trials.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Related Experiment Videos

Last Updated: Jun 15, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Area of Science:

Oncology
Molecular Biology
Drug Discovery

Background:

Polo-like kinase 4 (PLK4) is crucial for centriole biogenesis and synthetically lethal with TRIM37 gene amplification in cancer.
Previous PLK4 inhibitors faced challenges with selectivity and pharmacokinetic properties.
Centrinone B, a known inhibitor, exhibited metabolic instability and poor oral bioavailability.

Purpose of the Study:

To develop a potent and selective PLK4 inhibitor with improved drug-like properties.
To identify a novel therapeutic agent for TRIM37-amplified cancers.

Main Methods:

Structure-based drug design (SBDD) was employed to optimize Centrinone B.
Kinome profiling was conducted to assess selectivity against related kinases.
Preclinical studies evaluated RP-1664's pharmacokinetics, pharmacodynamics, and efficacy in xenograft models.

Main Results:

RP-1664 demonstrated significant improvements in potency, selectivity, and ADME properties compared to previous inhibitors.
Exquisite selectivity was observed over AURKA/B and PLK1 kinases.
RP-1664 effectively disrupted centriole biogenesis, showed target engagement in vivo, and demonstrated efficacy in TRIM37-amplified xenograft models.

Conclusions:

RP-1664 is a first-in-class clinical candidate targeting PLK4 for TRIM37-amplified cancers.
The optimized inhibitor exhibits favorable pharmacokinetics and potent anti-tumor activity.
RP-1664 is currently undergoing Phase 1 clinical trials for advanced solid tumors.