EZN-2968 / Enzon - LARVOL DELTA

Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer. (PubMed, Int J Mol Sci) - "Findings showcase the efficacy of agents like EZN-2968, Minnelide, and Acriflavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of HIF-1α mRNA modulation and antitumor activity. However, challenges, including toxicity, necessitate continued exploration and development, as exemplified by ongoing clinical trials. This article concludes by emphasizing the potential of targeted HIF therapies in disrupting cancer-related signaling pathways."

Journal • Review • Oncology • Von Hippel-Lindau Syndrome • HIF1A

First report of grapevine red globe virus, grapevine rupestris vein feathering virus and grapevine Syrah virus-1 infecting grapevine in Slovenia. (PubMed, Plant Dis) - "GRGV was amplified using specific primer pair RG6061F: 5'-CCGAGCTTCTCTCCAAGATCA-3' and RG6801R: 5'-ACTTAACGTAGGCCACTGGGT-3' (Cretazzo and Velasco 2017)...To our knowledge, this is the first report of GRGV, GRVFV and GSyV-1 infecting grapevine in Slovenia. Further analysis will be necessary to assess the prevalence of these viruses in Slovenian vineyards and to evaluate their impact on grapevine production."

Journal

Conditional Antisense Oligonucleotides Triggered by miRNA. (PubMed, ACS Chem Biol) - "As a proof-of-concept, we modified an HIF1α ASO (EZN2968) to generate miRNA-specific conditional ASOs, which can inhibit HIF1α in the presence of a hepatocyte-specific miRNA, miR-122, via a toehold exchange reaction...Using the same concept, we further generated another conditional ASO that can be triggered by miR-21. Our results suggest that conditional ASOs can be custom-designed with any miRNA to control ASO activation in targeted cells while reducing unwanted effects in nontargeted cells."

Journal • HIF1A • MIR122 • MIR21

A Pilot Study of EZN-2968, an Antisense Oligonucleotide Inhibitor of HIF-1alpha, in Adults With Advanced Solid Tumors With Liver Metastases (clinicaltrials.gov) - P1; N=10; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting ➔ Completed

Clinical • Trial completion • Hepatology • Oncology • Solid Tumor • HIF1A

Pilot trial of EZN-2968, an antisense oligonucleotide inhibitor of hypoxia-inducible factor-1 alpha (HIF-1α), in patients with refractory solid tumors (Cancer Chemother Pharmacol) - P1, N=10; NCT01120288; "Reduction in HIF-1α mRNA levels compared to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies. Reductions in levels of HIF-1α protein and mRNA levels of some target genes were observed in two patients. Quantitative analysis of DCE-MRI from two patients revealed changes in K trans and k ep. The trial was closed prematurely when the sponsor suspended development of this agent."

P1 data • Trial termination • Hepatocellular Cancer • Oncology