bortezomib

P2/3, N=0, Withdrawn, Regeneron Pharmaceuticals | N=1570 --> 0 | Not yet recruiting --> Withdrawn

Notably, ALLN significantly enhanced the sensitivity of MM cells to commonly used clinical drugs bortezomib and doxorubicin, while exhibiting no obvious cytotoxicity in normal cells. These findings establish CAPN2 as a promising therapeutic target in MM, with its inhibitor serving as a potential lead compound for further clinical evaluation. Our study also elucidates the relationship between hypercalcemia, CAPN2, and malignant proliferation in MM cells, and expands the therapeutic landscape for MM patients.

P2, N=24, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD-guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791.

P1, N=18, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Pharmacological studies, including activators, dual-target inhibitors, and bortezomib-bound structural complexes, support the potential ligandability of LONP1 but also highlight unresolved issues in selectivity, target engagement, mitochondrial toxicity, and context-dependent therapeutic windows. This review summarizes current structural, mechanistic, and pharmacological evidence for LONP1 as a context-dependent immunometabolic regulatory node and discusses limitations and open questions that must be addressed before clinical translation.

Anti-glioma effects with the lowest drug concentrations were achieved for proteasome inhibitors (carfilzomib, bortezomib, ixazomib), and HDAC inhibitors (panobinostat, romidepsin). The impact of their drug targets PSMB5 and HDAC1/2 on the growth of GBM cells was successfully validated by RNAi experiments. We established an aHTS platform for GBM TOs, and identified proteasome and HDAC inhibitors as promising drugs for the treatment of GBMs.

Moreover, insulin and IGF-II attenuated apoptosis and the inhibition of cell migration induced by the proteasome inhibitors (PIs) bortezomib and carfilzomib, and these effects were reversed by IFITM1 knockdown. The ability of insulin to reduce bortezomib-induced apoptosis and G2/M phase cell cycle arrest was likewise dependent on IFITM1 expression. Collectively, these findings suggest that insulin-induced IFITM1 plays a pivotal role in MM progression and resistance to bortezomib, highlighting IFITM1 as a potential prognostic biomarker and therapeutic target.

Cypripedin induces apoptosis in Jurkat T-ALL cells, synergizes with BTZ, and modulates ER stress through GRP78 ubiquitination. These findings support its further development as a potential T-ALL therapeutic.

P3, N=302, Active, not recruiting, GlaxoSmithKline | Trial completion date: Oct 2029 --> Jun 2029

P3, N=21, Active, not recruiting, GlaxoSmithKline | Trial completion date: Nov 2029 --> Jun 2029

P2, N=50, Completed, Australiasian Leukaemia and Lymphoma Group | Active, not recruiting --> Completed