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Chemical Structure| 96187-53-0 Chemical Structure| 96187-53-0

Structure of Brequinar
CAS No.: 96187-53-0

Chemical Structure| 96187-53-0

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Brequinar (DUP785) is a potent inhibitor of dihydroorotate dehydrogenase (DHODH) with an IC50 of 5.2 nM for human DHODH. Brequinar has potent activities against a broad spectrum of viruses.

Synonyms: DUP785; NSC 368390

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Product Citations

Product Citations

da Silva Emery, Flavio ; Vaidergorn, Miguel M ; Purificação, Aline D ; Leite, Pedro IP ; Silva-Mendonça, Sabrina ; Silva, Wemenes JL , et al.

Abstract: In response to the rising challenge of pathogen resistance to anti-infective therapies, innovative approaches such as host-directed therapy are being investigated to bypass these resistance mechanisms. Dihydroorotate dehydrogenase (DHODH) is a crucial enzyme for synthesizing pyrimidines, which are essential for RNA and DNA biosynthesis. Inhibiting DHODH can deplete the nucleotide pool, thereby impairing the replication of pathogens that depend on this pathway. In this study, we evaluated a library of fragment-like compounds against human DHODH (HsDHODH) and identified a 1,2-diarylethine scaffold as a potential new inhibitor. Utilizing the predicted binding mode and the activity of fragments 3a and 3l against HsDHODH, we designed and synthesized 14 novel diarylethine derivatives focused on improving their potency against the enzyme. The activity of the most potent compound (3e, IC50 1.50 ± 0.02µM) was translated to activity against SARS-CoV-2 in infected Calu-3 cells (EC50 1.7 ± 0.5µM), with low cytotoxicity. Early ADME in vitro evaluation indicated a need for improved solubility, which will be addressed in subsequent multi-parameter optimization efforts. These findings pave the way for developing novel HsDHODH inhibitors with enhanced pharmacological and pharmacokinetics profiles, offering a promising strategy to address viral diseases that are resistant to conventional treatments.

Keywords: Dihydroorotate dehydrogenase ; fragments ; antiviral ; host-directed therapy ; diarylethines

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Product Details of Brequinar

CAS No. :96187-53-0
Formula : C23H15F2NO2
M.W : 375.37
SMILES Code : O=C(C1=C(C)C(C2=CC=C(C3=CC=CC=C3F)C=C2)=NC4=CC=C(F)C=C14)O
Synonyms :
DUP785; NSC 368390
MDL No. :MFCD00866437
InChI Key :PHEZJEYUWHETKO-UHFFFAOYSA-N
Pubchem ID :57030

Safety of Brequinar

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
IMSCs 100 nM 7 days Evaluate the effect of BRQ on iMSCs survival, results showed iMSCs were highly tolerant to BRQ Front Cell Dev Biol. 2023 Feb 6;11:1089945.
HiPSCs (1231A3) 50 nM 7 days Evaluate the effect of BRQ on hiPSCs survival, results showed 50 nM BRQ completely eradicated hiPSCs Front Cell Dev Biol. 2023 Feb 6;11:1089945.

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Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.32mL

2.66mL

1.33mL

26.64mL

5.33mL

2.66mL

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