Targeting mitochondrial respiration with the complex I inhibitor carboxyamidotriazole orotate (CTO) redirected α-KG flux from mitochondrial sequestration, and increased α-KG-dependent m6A demethylation of MYC mRNA and HIF-1α hydroxylation. Combining CTO or α-KG dehydrogenase complex inhibitor devimistat with an α-KG analog (dimethyl α-KG) amplified c-Myc/HIF-1α suppression...Our work first identify a novel mechanism whereby mitochondrial metabolism drives systemic metabolic dysregulation in PDAC through the sequestration of α-KG, and establishes "redirecting α-KG flux from mitochondrial sequestration" as a strategy to disable PDAC's metabolic adaptability. The orotate salt form of carboxyamidotriazole effectively disrupts mitochondrial α-KG sequestration to suppresses PDAC growth at a dose equivalent to the clinically tested level.

In conclusion, we propose the iron-rifampicin complex as a potential candidate for nephroprotection against doxorubicin-induced nephrotoxicity, subject to further validation.

P3, N=235, Recruiting, Centre Hospitalier Universitaire de Nice | Not yet recruiting --> Recruiting | Trial completion date: Jul 2027 --> May 2028 | Trial primary completion date: Jul 2027 --> May 2028

P2, N=60, Recruiting, Children's Hospital of Philadelphia | Trial primary completion date: Dec 2026 --> Dec 2027

P3, N=422, Recruiting, Nantes University Hospital | Not yet recruiting --> Recruiting | Trial completion date: Jan 2031 --> Jun 2031 | Initiation date: Jan 2026 --> Jun 2026 | Trial primary completion date: Jul 2030 --> Dec 2030

While modulating Bcl-2 pathways can be effective in MS, future research should aim to provide greater clarification and to design precision-based drugs capable of neuroprotective effects.

Among 5 255 randomized patients, 374 (7.1%) had LTBI and received preventive treatment, most commonly isoniazid (82.1%) and rifampicin (11.8%). From Year 1-5 (after ~98% of LTBI+ patients completed preventive treatment), transaminase elevations were generally similar among LTBI+ and LTBI- patients. The absence of observed TB risk in guselkumab-treated patients suggests IL-23 inhibitors may be better treatment options than TNFi in high-risk patients, including those in TB-endemic regions.

Detection was carried out by multiple reaction monitoring mode using the transitions m/z 634.3→184.2 for golvatinib and m/z 650.3→200.2 for golvatinib N-oxide. Further study demonstrated that CYP3A4 was the principal enzyme involved in metabolizing golvatinib. To the best of our knowledge, this is the first report combining ultra-high-performance liquid chromatography-tandem MS (UHPLC-MS/MS) with UHPLC-Quadrupole-Orbitrap-HRMS for profiling golvatinib metabolism in vitro, thereby laying a foundation for subsequent pharmacokinetic study.

P2, N=42, Recruiting, Brigham and Women's Hospital | Trial completion date: Mar 2025 --> Jan 2027 | Trial primary completion date: Sep 2024 --> Jun 2026

P1/2, N=20, Completed, NexThera Co., Ltd. | Active, not recruiting --> Completed | N=30 --> 20

P2, N=30, Not yet recruiting, Georgetown University

P4, N=2174, Active, not recruiting, Duke University | Recruiting --> Active, not recruiting