Related Experiment Video
Updated: Feb 24, 2026
A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
Published on: January 27, 2026
Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition
Joseph T Madak1, Christine R Cuthbertson1, Wenmin Chen1
1Department of Medicinal Chemistry, College of Pharmacy, and Translational Oncology Program, University of Michigan, North Campus Research Complex, 1600 Huron Parkway, Ann Arbor, MI, 48109, USA.
Abstract:
Brequinar, a potent dihydroorotate dehydrogenase (DHODH) inhibitor, has been evaluated in multiple clinical trials as a potential treatment for cancer. To further understand brequinar-based DHODH inhibition and DHODH's therapeutic relevance in cancer, we have developed novel brequinar-based probes. We disclose a 16-step convergent synthesis of the first brequinar-PROTAC and a four-step approach towards the first mitochondrial-directed brequinar probe. A PROTAC and mitochondria-directed probe of brequinar both possess cytotoxicity that is superior to brequinar in a colony formation assay.
More Related Videos
03:38Aptamer-Based Target Detection Facilitated by a 3-Stage G-Quadruplex Isothermal Exponential Amplification Reaction
Published on: October 6, 2022
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
Related Concept Videos
01:28Structure-Activity Relationships and Drug Design
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
01:28Stability of Conjugated Dienes
A comparison of the enthalpies of hydrogenation of dienes reveals that conjugated dienes release less heat on hydrogenation, rendering them more stable than their nonconjugated analogs.
03:31Labeling DNA Probes
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...