carfilzomib

P2, N=80, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2028 | Initiation date: Jan 2026 --> Apr 2026 | Trial primary completion date: Feb 2026 --> Feb 2028

Background/Objectives: Carfilzomib (CFZ) and bortezomib (BTZ) are proteasome inhibitors used as the first-line therapy for relapsed or refractory multiple myeloma (MM) but are associated with cardiovascular adverse events (CVAEs). Pathway enrichment analyses identified peroxisome, MAPK, Rap1, adherens junction, phospholipase D, autophagy, and aldosterone-related pathways to be implicated in CVAEs. Our study identified distinct DMPs, DMRs, and pathways enrichment associated with CVAE, suggesting epigenetic contributors to CVAEs and supporting the need for larger validation studies.

A panel of human and murine breast cancer cell lines was treated with the IDH2 inhibitor AGI-6780, alone or in combination with the proteasome inhibitor carfilzomib (CFZ) or the E1 ubiquitin-activating enzyme inhibitor TAK-243. Inhibition of IDH2 markedly enhances the cytotoxic effects of proteasome-targeting by disrupting metabolic-proteostatic balance and promoting apoptotic cell death. These findings identify a growth-inhibitory effect that may be leveraged to improve functional dependency in breast cancer, particularly in triple-negative breast cancer, which currently lacks efficient drug treatments.

P3, N=525, Active, not recruiting, Bristol-Myers Squibb | Recruiting --> Active, not recruiting

P2, N=96, Suspended, Hackensack Meridian Health | Trial completion date: Jan 2026 --> Feb 2027 | Trial primary completion date: Jan 2026 --> Feb 2027

P3, N=508, Not yet recruiting, AstraZeneca

P2, N=17, Active, not recruiting, Mayo Clinic | Recruiting --> Active, not recruiting | N=75 --> 17

Gene enrichment analysis indicated pathways involving potassium channel regulation and thromboxane signaling to be implicated. This integrative metabolomic and genetic investigation supports a potential protective role of glycoursodeoxycholic acid in cardiovascular vulnerability and motivates larger, carfilzomib-specific studies to evaluate its utility for risk stratification.

P1, N=29, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2025 --> Dec 2026

Energy decomposition analysis identifies key interacting residues Pro171, Ile174, and Ala66 that anchor the inhibitors. Although both ligands induce subtle constriction of the channel pores, Bacopaside II establishes a more persistent hydrogen bonding network, underscoring its unique energetic contribution to the inhibition profile. Overall, these findings provide a detailed mechanistic blueprint for AQP1 inhibition by Bacopasides and offer a structural framework for the rational design of next-generation AQP1-targeted anticancer therapies.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Jun 2026 | Trial primary completion date: Jan 2026 --> Jun 2026

P3, N=915, Recruiting, Regeneron Pharmaceuticals | Not yet recruiting --> Recruiting