- |||||||||| vidofludimus (IMU-838) / Immunic
Journal: Carboxylic Acid Bioisosteres Boost Nurr1 Agonist Selectivity. (Pubmed Central) - Jul 17, 2025 Among them, the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus was found to exhibit strong Nurr1 agonism...We explored bioisosteric replacement of the drug's carboxylate motif and succeeded in boosting selectivity for Nurr1 over DHODH to >100-fold. Dopaminergic neural cells treated with the optimized tetrazole-based Nurr1 agonist revealed induction of genes involved in neuroprotection and neuronal health, supporting the potential of Nurr1 activation in neurodegenerative diseases.
- |||||||||| 4SC 301 / 4SC, acetylcysteine solution / Generic mfg.
Journal: ?-Hydroxybutyrate aggravates LPS-induced inflammatory response in bovine endometrial epithelial cells by activating the oxidative stress/NF-?B signaling pathway. (Pubmed Central) - Apr 12, 2025 As a representative antioxidant, N-acetylcysteine (NAC) treatment significantly reduced the phosphorylation of p65 and I?B in the BHBA and LPS co-treatment group...In summary, the current study demonstrates that BHBA aggravates LPS-induced inflammatory response in BENDs through the activation of oxidative stress/NF-?B signaling pathway, unravelling the mechanism by which BHBA exacerbates the inflammatory response in the BENDs of dairy cattle. This study elucidates the role of ketosis and its key metabolite BHBA in the pathogenesis of endometritis in dairy cows, providing valuable insights for understanding this pathological process.
- |||||||||| PCNA and histone deacetylase targeted inhibitors in cutaneous T-cell lymphoma (Section 16; Poster Board No: 21) - Mar 25, 2025 - Abstract #AACR2025AACR_6905;
Enhanced growth inhibition was also observed when AOH1996 was combined with other HDACi, such as domatinostat and panobinostat. These findings highlight the therapeutic potential of AOH1996 in combination with HDACi, particularly for CTCL, and pave the way for further exploration of this approach in cancer treatment.
- |||||||||| Rituxan (rituximab) / Roche
Trial completion, Trial completion date, Trial primary completion date: RITA: Rituximab and RASi in Patients with IgAN (clinicaltrials.gov) - Mar 17, 2025 P4, N=116, Completed, These findings highlight the therapeutic potential of AOH1996 in combination with HDACi, particularly for CTCL, and pave the way for further exploration of this approach in cancer treatment. Recruiting --> Completed | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Jul 2023 --> Mar 2024
- |||||||||| Zolinza (vorinostat) / Merck (MSD), domatinostat (4SC-202) / 4SC
Journal: Discovery of Novel 5-Cyano-3-phenylindole-Based LSD1/HDAC Dual Inhibitors for Colorectal Cancer Treatment. (Pubmed Central) - Nov 28, 2024 Compound 20c effectively modulated the expression of biomarkers associated with LSD1 and HDAC inhibition and demonstrated superior antiproliferative activity compared to SAHA and 4SC-202 across multiple colorectal cancer cell lines...It demonstrated significantly enhanced antitumor efficacy compared to SAHA, without causing observable toxicity. These findings highlight the potential of LSD1/HDAC dual inhibitors for the treatment of malignant cancers.
- |||||||||| 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
Targeting mitochondrial reactive oxygen species may offer therapeutic strategies for root surface remodeling or periodontal regeneration. 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.
- |||||||||| LOW DOSE DOUBLE EPIGENETIC THERAPY IMPROVES IMMUNOTHERAPY RESPONSE AND PROLONGS SURVIVAL IN PANCREATIC CANCER. (103AB - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_2386;
We previously showed, using the KPC (Kras LSL G12D/+; p53 r172H/+; Pdx1-Cre) mouse model of pancreatic cancer (PDAC), that sequential treatment with the DNA hypomethylating agent (HMA) decitabine (DAC) followed by aPD-1 initially enhanced anti-tumor effects, yet tumors developed resistance linked to a unique M2-polarized Chil3+ myeloid subtype...We then evaluated four different HDAC inhibitors with reported immunomodulatory effects and non-overlapping HDAC isoform specificities: Romidepsin (RM), Domatinostat (DM), Pracinostat (PR) and Entinostat (EN)...Our findings identify a functionally immune suppressive HMA specific myeloid effect. The addition of a second epigenetic agent enhances the therapeutic efficacy resulting in prolonged survival and reverses the suppressive myeloid cell related effects of DAC + aPD1.
- |||||||||| 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, SSR inhibits RIF by suppressing inflammatory response of hypoxia-exposed RTECs through PPAR?-mediated FAO. 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.
- |||||||||| Review, Journal, Combination therapy: Combination Therapy and Dual-Target Inhibitors Based on LSD1: New Emerging Tools in Cancer Therapy. (Pubmed Central) - Jan 26, 2024
Herein, we present a comprehensive overview of the combination of LSD1 inhibitors with various antitumor agents, as well as LSD1 multitarget inhibitors. Additionally, the challenges and future research directionsare also discussed, and we hope this review will provide new insight into the development of LSD1-targeted anticancer agents.
- |||||||||| KIO-101 / Kiora Pharma
Trial completion, Enrollment change: A Phase I Study of PP-001 Eye Drops in Healthy Adult Volunteers (clinicaltrials.gov) - Jan 12, 2024 P1, N=45, Completed, Vidofludimus is a candidate drug for the future threat of IAV H5N1 infection among humans as well as seasonal influenza virus infection. Unknown status --> Completed | N=24 --> 45
- |||||||||| KIO-101 / Kiora Pharma
Enrollment change, Trial completion date, Trial termination, Trial primary completion date: A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - Jan 11, 2024 P2, N=4, Terminated, Unknown status --> Completed | N=24 --> 45 N=132 --> 4 | Trial completion date: Nov 2024 --> Jan 2024 | Suspended --> Terminated | Trial primary completion date: Nov 2024 --> Jan 2024; Study halted prematurely but potentially will resume
- |||||||||| KIO-101 / Kiora Pharma
Trial completion date, Trial primary completion date: A Multi-Centre, Randomised, Controlled, Masked Phase 2 Study of the Safety and Efficacy of KIO-101 Ophthalmic Solution, Versus Vehicle Control in the Treatment of Dry Eye Disease in Patients With Autoimmune Disease (clinicaltrials.gov) - Dec 26, 2023 P2, N=132, Suspended, Triparanol and Fluphenazine reduced infectious viral loads in both Vero CCL81 and HBEC-5i cell cultures and, similar to the other validated compounds, are likely to exert antiviral activity through a molecular target in the host. Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte, Kinselby (resminostat) / 4SC, Yakult Honsha
Combination of JAKi and HDACi as a potential antiangionenic treatment in a Cutaneous T-cell Lymphoma (CTCL) in vivo chick embryo model () - Jul 24, 2023 - Abstract #EORTCCLTF2023EORTC_CLTF_101; Our results demonstrate that the direct anti-tumor effect of HDACi domatinostat on MCC cells is at least in part mediated via decreased HES1 expression allowing the induction of IFN?, which in turn causes apoptosis. Our results not only suggest the combination of ruxolitinib/ resminostat as a potential therapeutic combination for CTCL treatment but also establish a new dynamic in vivo model for the further investigation of the anti-angiogenic potential of different molecules used as anti-angiogenic drugs in the CTCL treatment.
- |||||||||| domatinostat (4SC-202) / 4SC
Trial completion date, Trial primary completion date, Combination therapy, Metastases: MERKLIN 2: Domatinostat in Combination With Avelumab in Patients With Advanced Merkel Cell Carcinoma Progressing on Anti-PD-(L)1 (clinicaltrials.gov) - Jul 13, 2023 P2, N=19, Active, not recruiting, Our findings suggest that domatinostat, which effectively targets the FOXM1-survivin axis required for the viability of ovarian cancer cells, is a promising option for the treatment of ovarian cancer. Trial completion date: Jul 2023 --> Dec 2024 | Trial primary completion date: Jul 2022 --> Feb 2024
- |||||||||| 4SC 301 / 4SC, Ledipasvir (GS-5885) / Gilead
Journal: In silico molecular study of hepatitis B virus X protein as a therapeutic target. (Pubmed Central) - May 31, 2023 The analysis of relative binding free energy through MM/GBSA for molecular dynamic simulation results revealed binding energy -9.9?kcal/mol for SC75741, -11?kcal/mol for Punicalagin, and -10.1?kcal/mol for Ledipasvir. These results elucidate the possible use of these compounds in the research for targeting HBx.Communicated by Ramaswamy H. Sarma.
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