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

P1, N=28, Recruiting, Immunic AG

P2/3, N=46, Recruiting, University of Guadalajara | Not yet recruiting --> Recruiting

P2/3, N=46, Not yet recruiting, University of Guadalajara | Trial completion date: Dec 2027 --> Jan 2027 | Trial primary completion date: Jun 2025 --> Dec 2026

Here, doxorubicin (DOX) and teriflunomide (Tfm) were used as therapeutic building blocks for the self-assembly of tumor-targeting, excipient-free nanoassemblies (DoT) that enhance ferroptosis induction in TNBC. Simultaneously, Tfm further devastated the intracellular ferroptosis defense system by suppressing DHODH and crippling the radical-trapping antioxidant capacity, thus evoking robust ferroptotic cell death in TNBC cells. The work presents a synergistic co-disruption strategy against dual ferroptosis defense systems, exhibiting significant potential for clinical applications.

P=N/A, N=110, Recruiting, Foundation University Islamabad

P=N/A, N=3, Terminated, University Hospital, Basel, Switzerland | N=15 --> 3 | Active, not recruiting --> Terminated; The study was prematurely terminated due to significant difficulties in recruiting participants, arising from the extremely rare nature of the targeted gene mutation.

BAY-2402234, a DHODH inhibitor, effectively kills pS6+ cells in vitro, with IC50 values correlating with pS6 signaling strength across 14 B-ALL patient-derived xenografts (PDX). In vivo, DHODH inhibition prolongs survival and reduces leukemia burden in pS6+ B-ALL models. These findings link active signaling to pyrimidine dependency and relapse risk, highlighting DHODH inhibition as a promising therapeutic strategy for chemo-resistant B-ALL.