Home Metabolism Dehydrogenase Remmer Brequinar (DUP785)

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Brequinar (DUP785) DHODH-remmer

Cat.nr.: S6626

Brequinar is een remmer van dihydroorotaat dehydrogenase (DHODH) met een IC50 van ~20 nM in vitro.
Brequinar (DUP785) Dehydrogenase Remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 375.37

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Kwaliteitscontrole (Quality Control)

Batch: Zuiverheid: 99.93%
99.93

Celkweek, behandeling & werkzame concentratie
(Cell Culture, Treatment & Working Concentration)

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
insect cells Function assay Inhibition of human recombinant DHODH expressed in baculovirus infected insect cells using dihydroorotate as substrate in presence of quinone by dichlorophenol-indophenol dye based assay, IC50=0.01μM 27994748
A549 Antiviral assay Antiviral activity against Yellow fever virus infected in human A549 cells assessed as reduction in virus replication, EC50=0.078μM 31557612
A549 Antiviral assay Antiviral activity against West Nile virus infected in human A549 cells assessed as reduction in virus replication, EC50=0.078μM 31557612
A549 Antiviral assay Antiviral activity against Dengue virus infected in human A549 cells assessed as reduction in virus replication, EC50=0.078μM 31557612
A549 Antiviral assay Antiviral activity against Western equine encephalomyelitis virus infected in human A549 cells assessed as reduction in virus replication, EC50=0.078μM 31557612
A549 Antiviral assay Antiviral activity against Vesicular stomatitis virus infected in human A549 cells assessed as reduction in virus replication, EC50=0.078μM 31557612
Jurkat Antiproliferative assay 72 hrs Inhibition of cell proliferation of human Jurkat cells incubated for 72 hrs by Celltiter-Glo assay, IC50=0.2μM 26079043
MDCK Antiviral assay 48 hrs Antiviral activity against VSV infected in MDCK cells assessed as inhibition of VSV replication after 48 hrs by plaque assay, EC50=0.3μM 23930152
MDCK Antiviral assay 48 hrs Antiviral activity against influenza A virus A/WSN/33 (H0N1) infected in MDCK cells after 48 hrs by plaque assay, EC50=0.46μM 23930152
HL60 Antiproliferative assay 72 hrs Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay, IC50=0.544μM 29727569
HCT116 Antiproliferative assay 72 hrs Antiproliferative activity against human HCT116 cells over-expressing DHODH after 72 hrs by MTT assay, IC50=0.679μM 29727569
Jurkat T Antiproliferative assay 72 hrs Antiproliferative activity against human Jurkat T cells assessed as DNA content after 72 hrs by Hoechst 33258 dye-based fluorescence assay, IC50=0.91μM 29939742
Jurkat T Antiproliferative assay 72 hrs Antiproliferative activity against human Jurkat T cells assessed as DNA content after 72 hrs by Hoechst 33258 dye based fluorometric method, IC50=0.93μM 28235702
MIAPaCa2 Antiproliferative assay 72 hrs Antiproliferative activity against human MIAPaCa2 cells after 72 hrs by MTT assay, IC50=1.69μM 29727569
Jurkat T Cytotoxicity assay 72 hrs Cytotoxicity against human Jurkat T cells assessed as compound concentration required to induce up to 30% cell death after 72 hrs by Hoechst 33258 dye based fluorometric method, Activity=45μM 28235702
Jurkat T Cytotoxicity assay 72 hrs Cytotoxicity against human Jurkat T cells assessed as compound concentration required to induce =>30% cell death after 72 hrs by CellTox green assay, Activity=48.2μM 29939742
HCT116 Growth inhibition assay 72 hrs Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay 29727569
HCT116 Cytostatic activity assay 10 uM 24 hrs Cytostatic activity against human HCT116 cells assessed as reduction in colony forming at 10 uM after 24 hrs by crystal violet staining based assay 29727569
HCT116 Cytostatic activity assay 10 uM 7 days Cytostatic activity against human HCT116 cells assessed as reduction in colony forming at 10 uM after 7 days by crystal violet staining based assay 29727569
U937 Antiproliferative assay 0.01 to 10 uM 3 days Antiproliferative activity against CFSE-labeled human U937 cells at 0.01 to 10 uM after 3 days by propidium iodide staining-based flow cytometry 29939742
THP1 Antiproliferative assay 0.01 to 10 uM 3 days Antiproliferative activity against CFSE-labeled human THP1 cells at 0.01 to 10 uM after 3 days by propidium iodide staining-based flow cytometry 29939742
U937 Function assay 0.1 to 10 uM up to 4 days Induction of myeloid differentiation in human U937 cells assessed as increase in CD11b expression level at 0.1 to 10 uM up to 4 days by propidium iodide staining-based flow cytometry 29939742
THP1 Function assay 0.1 to 10 uM up to 5 days Induction of myeloid differentiation in human THP1 cells assessed as increase in CD11b expression level at 0.1 to 10 uM up to 5 days by propidium iodide staining-based flow cytometry 29939742
THP1 Function assay 0.1 to 10 uM up to 5 days Induction of myeloid differentiation in human THP1 cells assessed as increase in CD14 expression level at 0.1 to 10 uM up to 5 days by propidium iodide staining-based flow cytometry 29939742
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit (Chemical Information, Storage & Stability)

Molecuulgewicht 375.37 Formule

C23H15F2NO2

 Opslag (vanaf de datum van ontvangst) 3 years -20°C powder
CAS-nr. 96187-53-0 -- Opslag van stamoplossingen

Synoniemen DUP785, NSC 368390 Smiles CC1=C(C2=C(C=CC(=C2)F)N=C1C3=CC=C(C=C3)C4=CC=CC=C4F)C(=O)O

Oplosbaarheid (Solubility)

In vitro
Batch:

DMSO : 37 mg/mL (98.56 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa Concentratie Volume Molecuulgewicht
Verdunningscalculator Molecuulgewichtcalculator

In vivo
Batch:

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

mg/kg g μL

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH2O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme (Mechanism of Action)

Targets/IC50/Ki
DHODH
20 nM
In vitro

Brequinar sodium (BQR) reduces of PyN levels in Con A-stimulated T cells and inhibition of cell proliferation at low concentrations, which can be reversed by uridine. However, uridine is unable to reverse the effects of high concentrations of BQR. BQR possesses the ability of inhibiting tyrosine phosphorylation.
In vivo

Brequinar sodium (BQR) induces anemia through inhibition of DHO-DHase activity and de novo pyrimidine synthesis in vivo. Coadministration of BQR with uridine prevents anemia.
Referenties

Informatie over klinische proeven (Clinical Trial Information)

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2023-11-07)

NCT-nummer Werving Aandoeningen Sponsor/medewerkers Startdatum Fasen
NCT05166876 TERMINATED
COVID-19
Clear Creek Bio, Inc.
 2022-02-01 PHASE2
NCT04575038 COMPLETED
COVID-19 Infection
Clear Creek Bio, Inc.
 2020-11-19 PHASE2
NCT03760666 TERMINATED
Acute Myeloid Leukemia
Clear Creek Bio, Inc.
 2018-12-20 PHASE1; PHASE2
NCT04425252 COMPLETED
COVID-19
Clear Creek Bio, Inc.
 2020-08-19 PHASE1; PHASE2
NCT03760666 Terminated
Acute Myeloid Leukemia
Clear Creek Bio Inc.
 2018-12-20 Phase 1|Phase 2