- |||||||||| izumerogant (IMU-935) / Immunic, Lagevrio (molnupiravir) / Ridgeback Biotherap, Merck (MSD)
Journal: Orally Bioavailable ROR?/DHODH Dual Host-Targeting Small Molecules with Broad-Spectrum Antiviral Activity. (Pubmed Central) - Nov 13, 2024 In a SARS-CoV-2 mouse model, treatment with a dual inhibitor alone, or in combination with molnupiravir, reduced the viral load by 7- and 58-fold, respectively. Considering the clinical safety, oral bioavailability, and tolerability of izumerogant in a recent Phase I study, izumerogant-like drugs represent potent dual-targeting antiviral HDAs with pronounced broad-spectrum activity for further clinical development.
- |||||||||| vidofludimus (IMU-838) / Immunic
Journal: Synthesis and Characterization of DHODH Inhibitors Based on the Vidofludimus Scaffold with Pronounced Anti-SARS-CoV-2 Activity. (Pubmed Central) - Jun 18, 2024 Thus, several DHODH inhibitors, including vidofludimus calcium (VidoCa, IMU-838), are currently in development or have been investigated in clinical trials for the treatment of virus infections such as SARS-CoV-2-mediated coronavirus disease 19 (COVID-19). Here, we report the medicinal chemistry optimization of VidoCa that resulted in metabolically more stable derivatives with improved DHODH target inhibition in various mammalian species, which translated into improved efficacy against SARS-CoV-2.
- |||||||||| Review, Journal: Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis. (Pubmed Central) - May 11, 2024
Here, we report the medicinal chemistry optimization of VidoCa that resulted in metabolically more stable derivatives with improved DHODH target inhibition in various mammalian species, which translated into improved efficacy against SARS-CoV-2. SPMS and PPMS are being studied for new treatments and future trials should consider combination therapies targeting inflammation, demyelination, and neuronal death, as the pathogenesis of PMS involves complex factors.
- |||||||||| vidofludimus (IMU-838) / Immunic
Trial completion date, Trial primary completion date: CALLIPER: Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients With Progressive Multiple Sclerosis (clinicaltrials.gov) - Apr 28, 2024 P2, N=450, Active, not recruiting, SPMS and PPMS are being studied for new treatments and future trials should consider combination therapies targeting inflammation, demyelination, and neuronal death, as the pathogenesis of PMS involves complex factors. Trial completion date: Jul 2024 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2025
- |||||||||| vidofludimus (IMU-838) / Immunic
Trial termination: CALDOSE-1: Phase 2 Dose-finding IMU-838 for Ulcerative Colitis (clinicaltrials.gov) - Mar 5, 2024 P2, N=263, Terminated, IMU-856 may offer extensive potential beyond celiac disease in other diseases, both intestinal and systemic, with compromised intestinal barrier function. Active, not recruiting --> Terminated; Considering the efficacy results of the induction phase (allowed use of corticosteroids as concomitant medication) in the study population and since IMU-838 did not show superiority over placebo, the OLE was prematurely closed by the sponsor.
- |||||||||| izumerogant (IMU-935) / Immunic
Enrollment change, Trial completion date, Trial termination, Trial primary completion date, Metastases: IMU-935 in Patients With Progressive, Metastatic Castration Resistant Prostate Cancer (clinicaltrials.gov) - Jan 17, 2024 P1, N=18, Terminated, Vidofludimus is a candidate drug for the future threat of IAV H5N1 infection among humans as well as seasonal influenza virus infection. N=42 --> 18 | Trial completion date: Dec 2023 --> May 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2023 --> May 2023; Lack of Efficacy
- |||||||||| vidofludimus (IMU-838) / Immunic
Preclinical, Journal: Development of a Potent Nurr1 Agonist Tool for In Vivo Applications. (Pubmed Central) - May 12, 2023 We have discovered considerable Nurr1 activation by the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus calcium and systematically optimized this scaffold to a Nurr1 agonist with nanomolar potency, strong activation efficacy, and pronounced preference over the highly related receptors Nur77 and NOR1. The optimized compound induced Nurr1-regulated gene expression in astrocytes and exhibited favorable pharmacokinetics in rats, thus emerging as a superior chemical tool to study Nurr1 activation in vitro and in vivo.
- |||||||||| IMU-366 / Immunic
Journal: First Report of Pectobacterium versatile Causing Diseases on Potato in Xinjiang Uygur Autonomous Region and Heilongjiang Province, China. (Pubmed Central) - Apr 21, 2023 Amplified 16S rDNA sequences from two isolates designated as ZRIMU1267 and ZRIMU1366 showed more than 99% sequence identity to P. versatile CFBP6051T type strain and the sequences were submitted to GenBank (accession numbers: OP476349, OP476350)...2022), while our study reports P. versatile strains that are able to cause multiple diseases on potatoes in Xinjiang Uygur Autonomous Region and Heilongjiang provinces of China. The results indicate that P. versatile might be widely distributed in northern China, and it is necessary to include cropping season and post-harvest strategies to control diseases caused by P. versatile.
- |||||||||| meropenem / Generic mfg., vidofludimus (IMU-838) / Immunic
Journal: The activity and mechanism of vidofludimus as a potent enzyme inhibitor against NDM-1-positive E. coli. (Pubmed Central) - Mar 15, 2023 It was demonstrated by molecular dynamic simulation, site-directed mutagenesis and biomolecular interaction that vidofludimus could interact directly with the key amino acids (Met67, His120, His122 and His250) and Zn in the active site of NDM-1, thereby competitively inhibiting the hydrolysis activity of NDM-1 on meropenem. In summary, vidofludimus holds promise as anNDM-1 inhibitor, and the combination of vidofludimus and meropenem has potential as a therapeutic strategy for NDM-1-mediated infections.
- |||||||||| salinomycin (HSB-1216) / Hillstream BioPharma, vidofludimus (IMU-838) / Immunic
FDA event, Preclinical, Journal: Hydrogel-Based Pre-Clinical Evaluation of Repurposed FDA-Approved Drugs for AML. (Pubmed Central) - Mar 2, 2023 AML patient samples were equally sensitive to Salinomycin in the 3D hydrogels and partially sensitive to Atorvastatin. Together, this confirms that AML cell sensitivity is drug- and context-specific and that advanced synthetic platforms for higher throughput are valuable tools for pre-clinical evaluation of candidate anti-AML drugs.
- |||||||||| vidofludimus (IMU-838) / Immunic
Enrollment closed, Enrollment change, Trial completion date, Trial primary completion date, Combination therapy: IONIC: IMU-838 and Oseltamivir in the Treatment of COVID-19 (clinicaltrials.gov) - Jul 12, 2022 P2, N=38, Active, not recruiting, Assessment in longer, larger trials is justified. Recruiting --> Active, not recruiting | N=120 --> 38 | Trial completion date: Jul 2021 --> Sep 2022 | Trial primary completion date: May 2021 --> May 2022
- |||||||||| vidofludimus (IMU-838) / Immunic
Trial primary completion date: CALDOSE-1: Phase 2 Dose-finding IMU-838 for Ulcerative Colitis (clinicaltrials.gov) - Apr 12, 2022 P2, N=263, Active, not recruiting, Combining Molnupiravir with DHODH inhibitors may thus improve available therapy options for COVID-19. Trial primary completion date: Jul 2022 --> Oct 2022
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