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Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition.
- Source :
- Chemistry - A European Journal; 10/9/2017, Vol. 23 Issue 56, p13875-13878, 4p
- Publication Year :
- 2017
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09476539
- Volume :
- 23
- Issue :
- 56
- Database :
- Complementary Index
- Journal :
- Chemistry - A European Journal
- Publication Type :
- Academic Journal
- Accession number :
- 125561067
- Full Text :
- https://doi.org/10.1002/chem.201702999