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.

Using proteomics and transcriptomic profiles, we identified wild-type IDH1 as a crucial metabolic enzyme upregulated in gemcitabine plus cisplatin chemotherapy (GP)-resistant NPC...The DHODH inhibitor BAY2402234 markedly sensitized NPC cells to chemotherapy. Clinically, a prognostic model based on DDR and ferroptosis signatures effectively predicted disease relapse risk post-chemotherapy in NPC. This study links DDR to ferroptosis defense via the IDH1/α-KG/ALKBH5/DHODH axis, suggesting DHODH inhibition as a promising therapeutic strategy to overcome chemoresistance in tumors harboring wild-type IDH1.

We demonstrate that BCOR-deficient cells have a heightened sensitivity to DHODH inhibitors such as brequinar and leflunomide, that are already in clinical use. Rather, DHODH's role in the electron transport chain, essential for mitigating reactive oxygen species, may be the physiological vulnerability that pushes BCOR-mutant cells toward cell death when DHODH is inhibited. DHODH inhibitors could be repurposed as targeted therapies for BCOR-mutant tumors, offering a promising strategy for precision medicine in AML and other cancers.

Consequently, combination therapies targeting DHODH and glutamine metabolism were synergistic in impairing PCa cell proliferation. Altogether, these results highlight DHODH as a metabolic vulnerability of AR-positive and AR-negative PCa cells by regulating central carbon and nitrogen metabolism.

It is a pyrimidine synthesis inhibitor that has an inhibiting effect of tumor necrosis factor alpha (TNF α) signaling. We present a case of with generalized pustular skin lesions after intake of leflunomide, which resemble a pustular exacerbation of a pre-existing psoriasis as well as a generalized pustular psoriasis.

P3, N=225, Active, not recruiting, F2G Biotech GmbH | Recruiting --> Active, not recruiting

P1, N=1, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2025 --> Nov 2026 | Trial primary completion date: Dec 2025 --> Nov 2026

P=N/A, N=50, Recruiting, King Chulalongkorn Memorial Hospital | Trial completion date: Jan 2026 --> Jul 2026 | Trial primary completion date: Sep 2025 --> Dec 2025

P=N/A, N=900, Recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2027 --> Nov 2028 | Trial primary completion date: Sep 2027 --> Nov 2028

Collectively, our findings demonstrate that ARS improves LEF responsiveness in RA by activating the cGMP-PKG pathway and suppressing TRAF6/NFATc1-mediated osteoclastogenesis. These mechanistic insights may provide a theoretical basis and experimental foundation for future clinical studies exploring combination strategies for patients with RA with a poor therapeutic response to LEF.

The study highlights the PyMet-pathway interactions and its role in chemoresistance, providing a strategy for targeting PyMet in cancer.