Related Experiment Video
Updated: Aug 14, 2026
11:34
High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
Published on: May 5, 2014
13.7K
Advancing the development of TRIP13 inhibitors: A high-throughput screening approach
Rae M Sammons1, Soma Ghosh2, Lacin Yapindi2
1Targeted Therapeutic Drug Discovery & Development Program, The University of Texas at Austin, Austin, TX, United States.
SLAS Discovery : Advancing Life Sciences R & D
|April 14, 2025
Summary
Researchers developed a new high-throughput screening assay to identify TRIP13 inhibitors for cancer therapy. Anlotinib emerged as a potent inhibitor, validating the assay for discovering novel cancer treatments targeting TRIP13.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- TRIP13 is a key mitotic checkpoint regulator overexpressed in cancers, correlating with poor outcomes.
- Targeting TRIP13 offers potential for treating therapy-resistant and Rb-deficient cancers.
- Lack of a robust high-throughput screening (HTS) assay has impeded TRIP13 inhibitor development.
Purpose of the Study:
- To develop a sensitive and automatable HTS assay for measuring TRIP13 activity.
- To identify novel TRIP13 inhibitors using the developed assay.
- To validate potential inhibitors for cancer therapy.
Main Methods:
- Development of a luminescence-based biochemical assay using the ADP-Glo detection system.
- High-throughput screening of kinase-focused inhibitors and a library of 4000 compounds.
- Validation of hits using cellular thermal shift assay (CETSA).
Main Results:
- The assay demonstrated high sensitivity, low background, and excellent performance (z'-factor > 0.85, S/B ratio ~6).
- Anlotinib was identified as the most potent TRIP13 inhibitor with an IC50 of 5 μM.
- CETSA confirmed anlotinib's direct binding to TRIP13.
Conclusions:
- A robust HTS assay for TRIP13 activity has been successfully developed.
- The assay facilitates the discovery of novel TRIP13 inhibitors, with anlotinib as a promising candidate.
- This work advances the therapeutic potential of targeting TRIP13 in cancer treatment.
