Article ID Journal Published Year Pages File Type
5630282 Journal of Neuroimmunology 2017 8 Pages PDF
Abstract

•RAM-589.555 is a water soluble, permeable compound, that specifically inhibits POL1.•RAM-589.555 induces apoptosis and suppresses lymphocytes proliferation and viability.•Oral administration of RAM589.555 delays EAE onset and reduced disease severity.

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).

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