Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Potent Anti-Glioblastoma Effects of Next-Generation MNK Inhibitors.

Cancers·2026
Same author

Dual Targeting of Nucleotidase-Dependent and -Independent Functions via PROTAC-Mediated CD73 Degradation.

Journal of medicinal chemistry·2026
Same author

Phase 1 evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205.

Clinical cancer research : an official journal of the American Association for Cancer Research·2026
Same author

Increased Glucose Availability Sensitizes Pancreatic Cancer to Macrophage-Targeting Immunotherapies.

Cancer research communications·2026
Same author

Development of a Direct-to-Biology Platform to Discover Potent MNK Inhibitors.

Journal of medicinal chemistry·2026
Same author

Household income and adverse childhood outcomes after prenatal myelomeningocele repair.

American journal of obstetrics & gynecology MFM·2026

Related Experiment Video

Updated: May 28, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.4K

Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).

Paige J Monsen1, Prashant V Bommi2, Arabela A Grigorescu3

  • 1Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.

Journal of Medicinal Chemistry
|February 13, 2025
PubMed
Summary

A novel proteolysis targeting chimera (PROTAC), NU227326, effectively degrades indoleamine 2,3-dioxygenase 1 (IDO1). This potent IDO1 degrader shows promise for treating glioblastoma and other cancers by overcoming immunosuppression.

More Related Videos

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.1K
Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
07:22

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

3.2K

Related Experiment Videos

Last Updated: May 28, 2025

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
05:33

High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

9.4K
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.1K
Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
07:22

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

3.2K

Area of Science:

  • Immunology
  • Oncology
  • Biochemistry

Background:

  • Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme crucial in tumor immune evasion.
  • Current IDO1 inhibitors targeting enzyme activity have shown limited clinical efficacy in cancer patients.
  • There is a critical need for therapeutics addressing both enzymatic and non-enzymatic immunosuppressive functions of IDO1.

Purpose of the Study:

  • To develop and characterize a novel proteolysis targeting chimera (PROTAC) for IDO1 degradation.
  • To optimize a lead PROTAC series for enhanced potency and efficacy against IDO1.
  • To evaluate the therapeutic potential of the optimized PROTAC in glioblastoma models.

Main Methods:

  • Rational structure-based optimization of a lead IDO1 PROTAC series.
  • In vitro assessment of PROTAC potency using glioblastoma cell lines (determining DC50).
  • Mechanistic studies investigating the ubiquitin-proteasome system-mediated degradation pathway.

Main Results:

  • Developed NU227326, a highly potent IDO1 PROTAC with a DC50 of 5 nM in human glioblastoma cells.
  • Demonstrated sustained IDO1 degradation for at least 2 days post-treatment.
  • Confirmed IDO1 degradation occurs via the ubiquitin-proteasome pathway.

Conclusions:

  • NU227326 represents a potent and effective PROTAC for IDO1 degradation.
  • This novel therapeutic strategy holds significant promise for treating glioblastoma and other cancers.
  • Further investigation of NU227326 in preclinical cancer models is warranted.