Pharmacologically induced proteolysis of histone deacetylase-6 attenuates influenza virus replication despite limited anti-tumor effects

Life Sciences, Journal Year: 2025, Volume and Issue: 363, P. 123401 - 123401

Published: Jan. 13, 2025

The protein deacetylase HDAC6 has been controversially linked to cancer cell proliferation and viral propagation. We analyzed whether a pharmacological depletion of with recent proteolysis-targeting chimera (PROTAC) kills tumor cells. show that low micromolar doses the cereblon-based PROTAC TH170, but not its inactive analog TH170E, induce proteasomal degradation HDAC6. elimination by TH170 does compromise leukemia growth survival, DNA integrity, stability selected cancer-relevant proteins. Increasing generates hook-effect on apoptosis-associated fragmentation Unlike specific evoke, this is apoptosis an accumulation acetylated histones. Thus, like inhibitors, degraders do leukemic death unless they are used in non-selective concentrations. Bioinformatic analyses 91 lymphoid, 37 myeloid, 125 lung cells which was deleted CRISPR-Cas9 corroborate these data. expressed various bronchus types. In human model, reduces influenza A virus replication dependent strain without compromising vitality. These data suggest pharmacologically amenable kinase-independent functions control replication. Eliminating could be promising anti-viral strategy benign impact host

Language: Английский

Therapeutic delivery – industry update covering October 2024

Therapeutic Delivery, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 6

Published: Feb. 17, 2025

This Industry Update covers the period from 1st October through to 31 2024 and is based on information sourced company press releases, scientific literature, patents, various news websites. month saw two biotech acquisitions being made by larger biopharma companies with Modifi Biosciences, a focussing development of novel small molecule anticancer therapeutics, acquired Merck, AbbVie acquiring Aliada Therapeutics, which focuses treatment central nervous system disorders. Elektrofi Archon Biosciences both announced new investments, respectively, support high concentration subcutaneous drug delivery technology for Antibody cages therapeutic applications. GSK Cambridge University five-year collaboration focusing kidney respiratory disease, Aeropump Resyca launch soft mist nasal that they have been jointly developing. UCB gained FDA approval higher dose its injectable drug, BIMZELX autoimmune disorders, continuous infusion Parkinson's Disease. Eisai it has completed submission version already approved therapy Alzheimer's Clinical research updates included Johnson announcing termination Phase III trial evaluating an implanted combination device bladder cancer, Lilly positive results modified dosing regimen Kisunla (donanemab).

Language: Английский

Age-associated changes in transcriptional elongation and their effects on homeostasis

Trends in Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский