Ninlaro (ixazomib)

P=N/A, N=482, Completed, Takeda | Active, not recruiting --> Completed

IXZ effectively inhibited LUAD tumor growth and may overcome platinum resistance. These findings warrant further investigation into the clinical role of IXZ alone or in combination with CBP or other chemotherapies in patients with LUAD.

Dual targeting of FLT3/SYK (TAK-659) and the proteasome (Ixazomib) showed strong synergy across genetically defined AML subsets, irrespective of FLT3 mutant status. These findings define a therapeutically targetable axis linking FLT3/SYK/β-catenin signaling to stress adaptation, provide a mechanistic basis for combinatorial targeting in high-risk AML. Trial registration: NCT04079738, Date of registration 03 September 2019.

P2, N=21, Terminated, Mayo Clinic | Trial completion date: Jun 2025 --> Jan 2026

P2, N=25, Completed, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Completed | N=55 --> 25

P2, N=42, Completed, University of Chicago | Active, not recruiting --> Completed

Motivated by promising clinical trial data for the combination of the histone deacetylase 6 (HDAC6) inhibitor ricolinostat with the proteasome inhibitor bortezomib in relapsed/refractory multiple myeloma (MM) patients, we engineered dual HDAC6/proteasome inhibitors...Deploying the HDAC6-selective phenyl-4-hydroxamic acid motif, and O-carbamoylated hydroxamates as hydroxamic acid surrogates, then grafting to the electrophilic boronic acid warhead of bortezomib/ixazomib, we discovered several dual HDAC6/proteasome inhibitors that were potent in cell-free assays, inhibiting the chymotrypsin-like (CL) proteasomal activity on par with that of bortezomib, and many compounds demonstrated selectivity for HDAC6 over HDAC1 as predicted. Moreover, several dual HDAC6/proteasome inhibitors were submicromolar inhibitors of MM cell growth. Of particular interest, AMC-3-030 with an O-(N-phenylcarbamoyl)-hydroxamate ZBG emerged as an exciting lead for further studies.

P1, N=24, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P=N/A, N=72, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting

P2, N=30, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

P4, N=100, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University | Trial completion date: Jul 2025 --> Jul 2028 | Trial primary completion date: Jun 2024 --> Jun 2026

P2, N=79, Active, not recruiting, Alliance Foundation Trials, LLC. | Trial completion date: Jul 2026 --> Jun 2027 | Trial primary completion date: Oct 2025 --> Dec 2026