发明名称 |
TREATMENT OF DISEASES CAUSED BY ABNORMAL LYMPHOCYTE FUNCTION WITH AN HDAC6 INHIBITOR |
摘要 |
An HDAC6 inhibitor (a compound of Formula I) is shown to reduce the pathogenesis associated with the B cell mediated autoimmune disease, systemic lupus erythematosus (SLE). Administration of a compound of Formula I attenuated many of the symptoms characteristic of SLE including splenomegaly, abnormal B cell differentiation, an increase in the number double-negative thymic T cells, an increase in the level of auto-antibodies such as anti-dsDNA, immune complex -mediated glomerulonephritis and an increase in inflammatory cytokine production. Treatment with a compound of Formula I also increased the number of the subject's splenic Treg cells while removing circulating auto-antibodies. Inhibition of HDAC6 altered bone marrow B cell differentiation by increasing the percentage of cells in the early-stage developmental fractions of both pro-and pre-B cells. These results demonstrate HDAC6 inhibition with a compound of Formula I can treat SLE disease by altering aberrant T and B cell differentiation. |
申请公布号 |
WO2015042418(A1) |
申请公布日期 |
2015.03.26 |
申请号 |
WO2014US56584 |
申请日期 |
2014.09.19 |
申请人 |
ACETYLON PHARMACEUTICALS, INC.;EDWARD VIA COLLEGE OF OSTEOPATHIC MEDICINE;VIRGINIA TECH INTELLECTUAL PROPERTIES, INC. |
发明人 |
REILLY, CHRISTOPHER, M.;GAFOOR, ABDUL;CAUDELL, DAVID, L.;REGNA, NICOLE L.;JARPE, MATTHEW |
分类号 |
A61K31/495;A61P7/00;A61P37/00 |
主分类号 |
A61K31/495 |
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