phacetoperane (NLS-3) / NLS Pharma - LARVOL DELTA

Human-derived NLS enhance the gene transfer efficiency of chitosan. (PubMed, Biosci Rep) - "Our results show that co-complexation and covalent ligation of the NLS peptide derived from IGFBP-3 to chitosan polyplexes yields a 2-fold increase in transfection efficiency, which was not observed for NLS peptide derived from IGFBP-5. These results indicate that the integration of IGFBP-NLS-3 peptides into polyplexes has potential as a strategy to enhance the efficiency of non-viral vectors."

Journal • Gene Therapies • IGFBP3

Ezrin interacts with L-periaxin by the "head to head and tail to tail" mode and influences the location of L-periaxin in Schwann cell RSC96. (PubMed, Biochim Biophys Acta Gen Subj) - "In the present study, we observed that L-periaxin and ezrin interacted in a "head to head and tail to tail" mode in SC RSC96 through NLS3 region of L-periaxin with F3 subdomain of ezrin interaction, and the region of L-periaxin (residues 1368-1461) with ezrin (residues 475-557) interaction...Ezrin could inhibit the self-association of L-periaxin, and ezrin overexpression in sciatic nerve injury rats could facilitate the repair of impaired myelin sheath. Therefore, the interaction between L-periaxin and ezrin may adopt a close form to complete protein accumulation and to participate in myelin sheath maintenance."

Head-to-Head • Journal

Methods for measuring HMGB1 release during immunogenic cell death. (PubMed, Methods Enzymol) - "The "retention using selective hooks" (RUSH) system in which a streptavidin-NLS3 fusion protein serves as a nuclear hook to sequester streptavidin-binding peptide (SBP) fused with HMGB1 and green fluorescent protein (GFP) allowed for synchronizing HMGB1 increase. Thus, exclusively in the presence of biotin, which liberates HMGB1-SBP-GFP from its nuclear hook, immunogenic cell death (ICD) inducers such as anthracyclines are able to cause the nucleo-cytoplasmic translocation of HMGB1-SBP-GFP. This system facilitates the identification of HMGB1 releasing agents in medium- to high-throughput screening assays."

Immunogenic cell death • Journal

Nucleo-cytoplasmic shuttling of Drosophila Hairless/Su(H) heterodimer as a means of regulating Notch dependent transcription. (PubMed, Biochim Biophys Acta Mol Cell Res) - "Here, we investigate the function of the predicted nuclear localization signals (NLS 1-3) and single nuclear export signal (NES) of co-repressor Hairless using GFP-fusion proteins, reporter assays and in vivo analyses using Hairless wild type and shuttling-defective Hairless mutants. We identify NLS3 and NES to be critical for Hairless function...Importantly, we reveal that Su(H) protein strictly follows Hairless protein localization. Together, we propose that shuttling between the nucleo-cytoplasmic compartments provides the possibility to fine tune the regulation of Notch target gene expression by balancing of Su(H) protein availability for Notch activation."

Journal

The sequential phosphorylation of PHF10 subunit of the PBAF chromatin remodeling complex determines different properties of the PHF10 isoforms. (PubMed, Biol Open) - "These two subclusters surround a sequence, which is predicted to be a nuclear localization sequence (NLS3)...Thus phosphorylation of PHF10 isoforms regulates their cell level, determining the rate of incorporation in PBAF. This may alter the pattern of PBAF regulated genes."

Journal

Identification of pharmacological agents that induce HMGB1 release. (PubMed, Sci Rep) - "...For this, we took advantage of the "retention using selective hooks" (RUSH) system in which a streptavidin-NLS3 fusion protein was used as a nuclear hook to sequestrate streptavidin-binding peptide (SBP) fused with HMGB1 and green fluorescent protein (GFP)...These agents induced ICD through a panoply of distinct mechanisms. Their effective action was confirmed by multiple methods monitoring nuclear, cytoplasmic and extracellular HMGB1 pools, both in cultured human or murine cells, as well as in mouse plasma."

Journal

NLS Pharmaceutics Ltd. (NLS) Announces Notice of Allowance of two new Patents in North America Covering Attention Deficit Hyperactivity Disorder (ADHD) and Narcolepsy further bolstering its Patent Portfolio (GlobeNewswire, NLS Pharmaceutics) - U.S. Patent Application No 15/913,481, entitled PHACETOPERANE FOR TREATING OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (inventors.. The allowed invention claims a method for treating ADHD with phacetoperane, in particular levophacetoperane, or a pharmaceutically acceptable salt thereof. 'It is hoped that phacetoperane will succeed methylphenidate at least because of its safety profile,' said Eric Konofal, MD, PhD. In addition, Canadian Patent No 2,825,275, entitled LAUFLUMIDE AND THE ENANTIOMERS THEREOF, METHOD FOR PREPARING SAME AND THERAPEUTIC USES THEREOF (inventor.. The allowed invention claims inventive concepts related to the use of lauflumide or the enantiomers thereof in the treatment of ADHD, narcolepsy or idiopathic hypersomnia.

Clinical • Commercial • Patent