P2, N=450, Active, not recruiting, Immunic AG | Trial completion date: Jul 2024 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2025

Additionally, TF treatment facilitated a reduction in the levels of apoptosis-related proteins while simultaneously augmenting the levels of Bcl2. Our findings indicate that TF administration effectively mitigates CORT-induced depression-like behaviors and reverses damage to oligodendrocytes and neurons in the hippocampus, suggesting TF as a promising candidate for depression.

P3, N=225, Recruiting, F2G Biotech GmbH | Trial completion date: Mar 2025 --> Nov 2025

P=N/A, N=26, Active, not recruiting, Turku University Hospital | Trial primary completion date: Dec 2023 --> Dec 2024

Moreover, the combination of POLQ inhibitor and ferroptosis inducer synergistically suppressed MGC-803 xenograft tumor growth and diminished metastasis. Our results identify a POLQ-mediated stemness and ferroptosis defense mechanism and provide a new therapeutic strategy for gastric cancer.

The negatively charged nanomedicine ensured good blood stability and high tumor accumulation, while the charge-reversal to positive in response to the acidic pH in the tumor microenvironment (TME) and lysosomes enhanced the uptake by tumor cells and lysosome escape, achieving accumulation in mitochondria. The subsequently released Na+ in mitochondria not only contributed to the formation of mitomiR-494 induced G-quadruplexes for AIE imaging diagnosis but also led to an osmolarity surge that was enhanced by brequinar to achieve effective ion-interference therapy.

P1, N=1, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=18, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting

These findings highlight DHODH as a potential therapeutic target for treating ATL.

P=N/A, N=10, Active, not recruiting, Zuyderland Medisch Centrum | Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Aug 2024 | Trial primary completion date: Mar 2024 --> Jul 2024

P2, N=263, Terminated, Immunic AG | 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.

Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration with and highlighted, for the first time, dysregulation in Nrf2/NF-κB signaling.

P1, N=155, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2023 --> Jul 2024 | Trial primary completion date: Dec 2023 --> Jul 2024

P1, N=11, Terminated, University of Chicago | N=20 --> 11 | Recruiting --> Terminated; Terminated by PI

P1, N=40, Recruiting, Aurigene Discovery Technologies Limited | Not yet recruiting --> Recruiting

P2, N=20, Recruiting, N.N. Petrov National Medical Research Center of Oncology

P1, N=45, Completed, Panoptes Pharma GmbH | Unknown status --> Completed | N=24 --> 45

P2, N=4, Terminated, Kiora Pharmaceuticals, Inc. | 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

P2, N=38, Recruiting, The Deutsche Diabetes Forschungsgesellschaft e.V. | Trial completion date: Sep 2022 --> Jun 2025 | Trial primary completion date: Jun 2022 --> Jun 2024

P2, N=40, Recruiting, Peking University People's Hospital

P1/2, N=2, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P2, N=450, Active, not recruiting, Immunic AG | Recruiting --> Active, not recruiting

Pharmacologic inhibition of Cdk4 along with the downstream pyrimidine synthesis enzyme dihydroorotate dehydrogenase synergistically inhibits proliferation and survival of hepatocellular carcinoma cells. These studies demonstrate that cyclin D1 promotes a broad network of biosynthetic pathways in hepatocytes, and this model may provide insights into potential metabolic vulnerabilities in cancer cells.

P=N/A, N=400, Recruiting, University Hospital, Montpellier

P2, N=96, Recruiting, Algiax Pharmaceuticals GmbH

P1, N=24, Recruiting, Deborah Doroshow | Phase classification: P1a/1b --> P1

The nanomedicine (ATO/SRF@BSA) was developed by loading sorafenib (SRF) and atovaquone (ATO) into bovine serum albumin (BSA). Furthermore, the anti-cancer results showed that ATO/SRF@BSA exhibited tumor-specific killing efficacy, significantly improved the tumor hypoxic microenvironment, and lessened the toxic side effects of SRF. This work presents an efficient and easily achievable strategy for TNBC treatment, which may hold promise for clinical applications.

P2, N=132, Suspended, Kiora Pharmaceuticals, Inc. | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2023 --> Nov 2024

P2, N=124, Recruiting, Peking University People's Hospital

P2, N=132, Recruiting, Peking University People's Hospital

P2, N=60, Recruiting, ASLAN Pharmaceuticals | Phase classification: P2a --> P2 | Trial completion date: Apr 2024 --> Oct 2024 | Trial primary completion date: Feb 2024 --> Sep 2024

Here we show, in three mouse models of established ulcerative colitis, that a subcutaneously injected colon-specific immunosuppressive niche consisting of colon epithelial cells, decellularized colon extracellular matrix and nanofibres functionalized with programmed death-ligand 1, CD86, a peptide mimic of transforming growth factor-beta 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and reduced inflammation in the animals' lower gastrointestinal tract. The bioengineered colon-specific niche triggered autoreactive T cell anergy and polarized pro-inflammatory macrophages via multiple immunosuppressive pathways, and prevented the infiltration of immune cells into the colon's lamina propria, promoting the recovery of epithelial damage. The bioengineered niche also prevented colitis-associated colorectal cancer and eliminated immune-related colitis triggered by kinase inhibitors and immune checkpoint blockade.

P2, N=1, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Acupuncture stimulation can improve the degree of joint inflammation and swelling in CIA rats, which may be related to its effects in inhibiting the overexpression of immunoinflammatory factors in serum and regulating expression of mt-p53, NF-κB p65, PPARγ mRNAs and proteins in the synovial tissue.

I then apply emerging concepts in redox homeodynamics to discuss how the rewiring of the Krebs cycle and ETC promotes shifts in the RST to favor high rates of HO generation for cell signaling. This discussion then focuses on proline dehydrogenase (PRODH) and dihydroorotate dehydrogenase (DHODH), two enzymes over expressed in cancers, and how their link to one another through the coenzyme Q (CoQ) pool generates a redox connection that forms a HO signaling platform and pyrimidine synthesome that favors a hyper-proliferative state and disables ferroptosis.

P=N/A, N=400, Recruiting, University Hospital, Montpellier | Not yet recruiting --> Recruiting

Furthermore, the in vivo studies revealed that BQR@MLipo could remarkably accumulate into the bladder tumor and successfully initiate the infiltration of CD8 T cells into tumor microenvironment for enabling efficient CBI to inhibit bladder tumor growth. Therefore, BQR@MLipo may represent a clinically promising modality for enhancing CBI in bladder tumor.

Among the most promising MM SOC agents is monoclonal antibodies (mAb) such as the CD38 antibody daratumumab, which significantly improved the management of newly diagnosed and relapsed/refractory MM...We further verified HOSU-53 efficacy using the disseminated MM1.S luciferase CDX model and found a significant prolonged survival in the HOSU-53 cohort (median survival53-days) compared to vehicle (median survival28-days) that was further enhanced with isatuximab combination resulting in superior survival benefit (median survival 69-days)...Currently there is significant clinical interest in CD47 antibody therapy such as magrolimab for both solid tumors and hematological malignancies...In summary, we show compelling survival benefit for HOSU-53 as a monotherapy which is further enhanced when combined with anti-CD38 or anti-CD47 therapies. HOSU-53 is expected to enter phase 1 clinical trials in 2024 and our data is supportive for its expansion into MM.

Preliminary results from in vivo experiments using p53 deficient patient derived xenografts indicate that the combination of Orludodstat and Berzosertib is well tolerated, while significantly delaying leukemic growth (Figure 1 B). ConclusionTogether, our findings suggest that the combined targeting of de novo pyrimidine synthesis and ATR signaling may present a specific and non-genotoxic vulnerability for TP53 aberrant ALL.

Z-VAD-FMK (an apoptosis inhibitor) partially rescued blockade of DHODH-induced death of ESCC cells, and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) together with the necroptosis inhibitor (necrostatin-1) partially rescued inhibition of DHODH-induced death of CRC cells, respectively. Pathways including rheumatoid arthritis, salmonella infection, cytokine-cytokine receptor interaction, pertussis, and nuclear factor-κB (NF-κB) were enriched in DHODH-silenced ESCC cells. Overexpression of DHODH augments cell proliferation and suppresses cell death in ESCC and CRC, and DHODH might be developed as a potential anticancer target.