Vidofludimus (Vido) is a novel oral immunomodulatory drug that inhibits dihydro-orotate dehydrogenase and lymphocyte proliferation in vitro. Ex vivo Vido completely blocked IL-23 + IL-1β-stimulated secretion of IL-17 by colonic strips. In vivo Vido treatment alone most effectively reduced macroscopic and histological pathology and the numbers of CD3+ T cells[3]. Vidofludimus is 2.6 times more potent in inhibiting DHO oxidation by human DHODH (dihydroorotate dehydrogenase) compared to teriflunomide. The potency or vidofludimus to inhibit rat or mouse DHODH is 7.5 and 64.4 time lower than the for the human DHODH, respectively[4]. Moreover, vidofludimus also possesses remarkable beneficial effects in reducing NAFLD (Non-alcoholic fatty liver disease) by targeting FXR(farnesoid X receptor) [5].
Vidofludimus 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK293T cells
0.4±0.2 μM
16 hours
Evaluate the activation effect of Vidofludimus on Nurr1, showing significant agonist activity
J Med Chem. 2023 May 11;66(9):6391-6402.
HEK293T cells
10 μmol/L
72 hours
Evaluate the inhibitory effect of Vidofludimus on HEV replication, results showed significant inhibition of HEV replication
Virol Sin. 2024 Feb;39(1):123-133.
HuH7 cells
10 μmol/L
72 hours
Evaluate the inhibitory effect of Vidofludimus on HEV replication, results showed significant inhibition of HEV replication
Virol Sin. 2024 Feb;39(1):123-133.
Huh-7 cells
20 μM
48 hours
To evaluate the antiviral activity of Vidofludimus against SLEV in Huh-7 cells. Results showed no significant antiviral activity at 20 μM.
Louis Encephalitis Virus. Viruses.
HBEC-5i cells
20 μM
48 hours
To evaluate the antiviral activity of Vidofludimus against SLEV in HBEC-5i cells. Results showed no significant antiviral activity at 20 μM.
Louis Encephalitis Virus. Viruses.
Vero CCL81 cells
20 μM
72 hours
To evaluate the inhibitory effect of Vidofludimus on SLEV-induced cytopathic effects. Results showed that Vidofludimus inhibited SLEV-induced cytopathic effects at 20 μM.
Louis Encephalitis Virus. Viruses.
Porcine alveolar macrophages (PAMs)
1-10 μM
48 hours
Assess the anti-PRRSV activity of Vidofludimus in PAMs, showing significant dose-dependent inhibition
Vet Res. 2023 Dec 20;54(1):124.
Marc-145 cells
1-10 μM
48 hours
Evaluate the inhibitory effect of Vidofludimus on PRRSV replication, showing dose-dependent antiviral activity
Vet Res. 2023 Dec 20;54(1):124.
MEF cells
5 µM
1 hour
To investigate the FXR-dependent inhibitory effect of Vidofludimus on TNFα-induced IκBα degradation and nuclear p65 levels. Results showed that Vidofludimus significantly stabilized IκBα and inhibited nuclear p65 levels in WT MEFs, while these effects were substantially reduced in FXR KO MEFs.
Front Pharmacol. 2020 May 14;11:590.
HepG2 cells
5 µM
1 hour
To investigate the inhibitory effect of Vidofludimus on TNFα-induced IKKα/β phosphorylation and IκBα degradation. Results showed that Vidofludimus suppressed TNFα-induced phosphorylation of IKKα/β in a concentration-dependent manner, thereby inhibiting the degradation of IκBα protein.
Front Pharmacol. 2020 May 14;11:590.
PBMCs
2.1 µM
7 days
Evaluate the antiviral activity of Vidofludimus against HIV-1, showing effective inhibition of viral replication
Viruses. 2020 Dec 5;12(12):1394.
Huh7 cells
5.9 µM
24 hours
Assess the antiviral activity of Vidofludimus against HCV, showing effective inhibition of viral replication
Viruses. 2020 Dec 5;12(12):1394.
HFF cells
7.4 µM
7 days
Evaluate the antiviral activity of Vidofludimus against HCMV, showing effective inhibition of viral replication without detectable cytotoxicity
Viruses. 2020 Dec 5;12(12):1394.
Vidofludimus 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Female Sprague Dawley rats
Oral
5 mg/kg
Single dose, observed for 8 hours
Evaluate the pharmacokinetic properties of Vidofludimus, showing good bioavailability and plasma concentration
J Med Chem. 2023 May 11;66(9):6391-6402.
Mice
DSS-induced colitis model
Oral
20 mg/kg/day
Once daily until the end of the experiments
To investigate the therapeutic effects of Vidofludimus on DSS-induced colitis and its FXR-dependency. Results showed that Vidofludimus significantly ameliorated DSS-induced colitis as assessed by reduced body weight loss, prevented colonic shortening, and decreased histological scores in WT mice, while these effects were not observed in FXR KO mice.
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