title: RAM-589.555 a new Polymerase-1 inhibitor as innovative targeted-treatment for multiple sclerosis.
abstract: Targeting Polymerase-1 (POL1) transcription machinery is a new strategy for suppression of multiple sclerosis (MS) disease activity that is based on suppression of ribosomal biogenesis and subsequent activation of apoptosis. We developed an oral POL1 inhibiting compound RAM-589.555, that suppress ribosomal biogenesis as an innovative therapeutic approach to ameliorate MS. RAM-589.555 shows high permeability, specificity to POL1 pathway, ability to induce apoptosis and to inhibit proliferation and viability of activated lymphocytes both in-vitro and in-vivo. Moreover, oral administration of RAM-589.555 blocks ribosomal RNA transcription and significantly suppresses and ameliorates experimental autoimmune encephalomyelitis (EAE).
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Sackler School of Medicine, Tel-Aviv University, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Achiron
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Zilkha-Falb
authors.affiliation: Department of Chemistry, Ben-Gurion University of the Negev, Be'er-Sheva, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Mashiach
authors.affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. Electronic address: gurevich@sheba.health.gov.il.
authors.forename: M
authors.initials: M
authors.lastname: Gurevich
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000737:chemistry; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000639:trends*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D009287:Naphthyridines / Q000008:administration & dosage* / Q000737:chemistry; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; C557717:CX 5461; D009287:Naphthyridines; D012318:RNA Polymerase I
keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; Polymerase-1 inhibitor