Semi-quantitative histological scoring confirmed that LEES effectively limited articular structural damage without inducing the hepato-splenic toxicity associated with methotrexate. These findings indicate that LEES possesses multimodal immunomodulatory and analgesic actions with a highly favorable tolerability profile, supporting its further preclinical development as a potential adjunct or alternative to existing therapies.

Therefore, in the present study, a multifunctional nanoplatform, hollow mesoporous manganese dioxide (H-MnO2)-hemin-leflunomide@membrane (MHL@M), is proposed and fabricated...Both in vitro and in vivo results demonstrate that MHL@M has excellent tumor-targeting, TME-responsive, and ferroptosis activation capacities. This study provides a solid foundation for the development of ferroptosis-based therapeutic strategies for GBM.

These findings highlight TER as a promising immune checkpoint modulator that targets the PD-1/PD-L1 axis to promote CD8+ T-cell-mediated antitumor immunity. Because of its established safety profile, TER is a readily translatable therapeutic for enhancing cancer immunotherapy in CRC.

P1/2, N=17, Completed, Joseph Sparano | Active, not recruiting --> Completed

P1, N=26, Not yet recruiting, Immunic AG

P=N/A, N=3500, Active, not recruiting, Sanofi | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Nov 2025 --> Mar 2026

Additionally, Brequinar, a de novo pyrimidine synthesis inhibitor, was used to verify the role of pyrimidine metabolism...The molecular docking results demonstrated that Eupatilin, 5,6,7,8-Tetramethoxyflavone, and 5-Hydroxy-6,7,3',4',5'-Pentamethoxyflavone exhibited potential interactions with the hub targets TP53, IL6, and TNF. Liubao tea attenuates OA progression by modulating the composition of the gut microbiota and inhibiting the pyrimidine metabolism pathway, highlighting its potential as a novel natural therapeutic agent for OA.

P2, N=27, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=56 --> 27 | Trial completion date: Jul 2026 --> Jan 2027 | Trial primary completion date: Jul 2026 --> Jan 2027

This work reveals for the first time that brequinar (BQR, a DHODH inhibitor) exerts dual-edged effects on ferroptotic therapy against 4T1 cells: besides its well-known disruption of cellular redox balance for ferroptosis sensitization, BQR-intervened pyrimidine metabolism blocks tumor growth, accompanied by up-regulation of lipid droplets (LDs), which paradoxically aggravates ferroptosis resistance...This work helps to accelerate DHODH inhibitors' clinical translation by elucidating previously overlooked mechanisms limiting DHODH inhibitors' efficacy and proposing synchronous DGAT1 inhibition as a countermeasure. The fabricated nanoweapon AB@HA-TA/Fe presents a novel dual metabolic intervention paradigm for ferroptosis sensitization, proposing an innovative framework for ferroptosis-integrated combination therapy of TNBC.

P1, N=24, Active, not recruiting, Immunic AG | Recruiting --> Active, not recruiting

P3, N=1121, Active, not recruiting, Immunic AG | Recruiting --> Active, not recruiting | Trial completion date: Sep 2032 --> Sep 2033 | Trial primary completion date: Sep 2024 --> Nov 2026

P3, N=1100, Active, not recruiting, Immunic AG | Recruiting --> Active, not recruiting | Trial completion date: Oct 2032 --> Oct 2033 | Trial primary completion date: Oct 2024 --> Nov 2026