mitoxantrone

P2, N=22, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2029 --> May 2029 | Trial primary completion date: May 2027 --> Jan 2026

P4, N=289, Recruiting, Medizinische Hochschule Hannover | N=128 --> 289

Collectively, our findings establish TSPAN6 as a migrasome-related regulator driving adverse immunotherapy outcomes and responses. Targeting TSPAN6, potentially with mitoxantrone, presents a potential strategy to enhance immunotherapy efficacy.

P4, N=128, Recruiting, Medizinische Hochschule Hannover | N=52 --> 128

P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Jun 2029

Compound 30, but not 16 or 40, sensitized ABCG2-expressing HEK-293-R5 cells to mitoxantrone. Distinct docking modes of compounds 30 and 40 to ABCG2 predict the structural determinants for the inhibition of ATPase. These results reveal novel rigid, extended nucleoside inhibitors of ABC transporters with varied activities that attenuate MDR in cells.

P2/3, N=765, Not yet recruiting, Charite Universitaetsmedizin Berlin KR

Adverse events during induction and reinduction were consistent with those reported in previous infant acute lymphoblastic leukaemia studies. Infections remain a substantial cause of morbidity and mortality in this immunocompromised patient population and extended beyond the induction and reinduction chemotherapy phases.

Furthermore, the same trajectories were used for the Binding Free and Total Complex Energies computations, revealing that the complexes were stable. All the studies, from protein energies to docking to simulation and binding free energy, supported the stable complexes; however, experimental studies are necessary before their use.

The novel carborane-containing N-carboranyl isoquinolinones were evaluated for cytotoxicity, ABCG2 inhibition, and reversal of MDR in combination with mitoxantrone (MXN) in an ABCG2-expressing Madin-Darby canine kidney II cell model...Especially, the 4-methoxyphenyl- and 3,4-dimethoxyphenyl-substituted isoquinolinones (IC-10, IC-11) caused the strongest left shift of the MXN IC50 value by 8.1- and 7.2-fold, indicating effective resensitization to the chemotherapeutic agent. Therefore, carborane-containing isoquinolinones featuring additional methoxy groups represent a promising approach for the development of ABCG2 inhibitors to overcome resistance to anticancer drugs.

Taken together, our results identify a distinct type of ribosome-enriched SGs that form through RNA-ribosome condensation rather than classical translational stress pathways. This mechanism provides a direct example of how a clinically used drug can reorganize cytoplasmic RNA-protein complexes, with possible consequences for mRNA regulation, cancer therapy, and neurodegenerative disease.

These findings demonstrate that PPA is unlikely to be a substrate of ABCG2 but functionally inhibits ABCG2-mediated efflux, contributing to the restoration of MTX sensitivity, although there may be additional mechanisms involved. PPA could be a promising MDR-reversal agent in ABCG2-driven chemotherapy resistance.