P1, N=12, Completed, Nanfang Hospital of Southern Medical University; Shionogi & Co., Ltd.

P2, N=300, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Feb 2024 --> Apr 2025

P=N/A, N=900, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

P3, N=200, Not yet recruiting, University Hospital, Strasbourg, France

P2, N=99, Completed, Algiax Pharmaceuticals GmbH | Recruiting --> Completed | Trial completion date: Mar 2025 --> Oct 2024

P2, N=70, Recruiting, Ain Shams University

P1/2, N=12, Completed, Panoptes Pharma GmbH | Unknown status --> Completed | N=18 --> 12

Moreover, combined treatment with TRF and daunorubicin (DNR) significantly reduced cell viability and promoted apoptosis in DNR-resistant T-ALL cells. Our study provides valuable insights into the critical role of TRF in treating T-ALL while increasing the sensitivity of DNR-resistant T-ALL cells to DNR.

P=N/A, N=10, Completed, Zuyderland Medisch Centrum | Active, not recruiting --> Completed

P=N/A, N=188, Not yet recruiting, Dongzhimen Hospital, Beijing University of Chinese Medicine; Dongzhimen Hospital, Beijing University of Chinese Medicine

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Aug 2024 --> Nov 2024 | Trial primary completion date: Aug 2024 --> Nov 2024

P1, N=153, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

Human stromal cell lines HS-5 and HS-27, as well as primary MSCs isolated from patient bone marrow, were superior in promoting AML differentiation compared to mouse cells in response to AICAr and brequinar, with the inhibitors not significantly affecting the stromal cells themselves. In conclusion, our study highlights the supportive role of human BM MSCs in enhancing the differentiation effects of pyrimidine synthesis inhibitors on AML cells, suggesting that AML treatment strategies focusing on differentiation rather than cell killing may be successful in clinical settings.

Here, we rationally designed a hollow iron-doped SiO2-based nanozyme (FeSHS) loaded with brequinar (BQR) and lificiguat (YC-1), named FeSHS/BQR/YC-1-PEG, for tumor ferroptosis activation...The elevation of levels of iron and PUFAs while simultaneously disrupting the GPX4/DHODH/FSP1 inhibitory pathways by our designed nanoplatform displayed high therapeutic efficacy both in vitro and in vivo. This work elucidates rationally designing smart nanoplatforms for ferroptosis activation and future tumor treatments.

P3, N=166, Completed, Genzyme, a Sanofi Company | Trial completion date: Jun 2025 --> Jul 2024 | Active, not recruiting --> Completed

Leflunomide has been shown to reduce body weight but also increase blood pressure...Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts.

P=N/A, N=900, Not yet recruiting, Novartis Pharmaceuticals

P2, N=29, Recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Feb 2027 | Trial primary completion date: Jun 2024 --> Feb 2027

P2, N=203, Completed, F2G Biotech GmbH | Recruiting --> Completed | Phase classification: P2b --> P2

P1/2, N=2, Completed, City of Hope Medical Center | Terminated --> Completed

In vivo studies demonstrated synergetic tumor growth inhibition in xenograft models with brequinar and venetoclax combination treatment. These results provide preliminary evidence for the rational combination of DHODH and BCL2 blockade in HGBCL with abnormal MYC and BCL2.

P2, N=96, Recruiting, Algiax Pharmaceuticals GmbH | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Apr 2024 --> Jan 2025

P1, N=19, Recruiting, City of Hope Medical Center

P3, N=225, Recruiting, F2G Biotech GmbH | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=56, Recruiting, City of Hope Medical Center | N=20 --> 56 | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=2, Terminated, City of Hope Medical Center | Trial completion date: Jun 2024 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Jun 2023; Accrual rate is too slow.

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