ITF2357

Uses

Givinostat Hydrochloride Hydrate is a potent inhibitor of HDAC with IC50?of 7.5-16 nM. It is used in the treatment of muscular dystrophy.

Uses

Givinostat hydrochloride hydrate has been used as a histone deacetylase inhibitor to test its effect on the human immunodeficiency virus reactivation in CD4⁺ T-cell model.

Biological Activity

itf2357, also known as givinostat, is a potent inhibitor of both class i and class ii histone deacetylase (hdac) as well as a potent inhibitor of hematopoietic colony formation by jakev617f-bearing progenitor cells from chronic myeloproliferative neoplasms in vitro. previous studies has shown that itf2357 induces apoptosis of multiple myeloma (mm) and acute myelogenous leukemia (aml) cells following induction of p21 and down-modulation of bcl-2 and mcl-1 proteins and inhibits the production of pro-inflammatory cytokines (such as il-1, il-6, tumor necrosis factor (tnf)-α and interferon (ifn)-γ) by peripheral blood mononuclear cells as well as the production of il-6 and vascular endothelium growth factor (vegf) by mesenchymal stromal cells.katia todoerti, valentina barbui, olga pedrini, marta linett, gianluca fossati, paolo mascagni, alessandro rambaldi, antonino neri, martino introna, luigia lombardi, and josee golay. pleiotropi anti-myeloma activity of itf2357: inhibition of interleukin-6 receptor signaling and repression of mir-19a and mir-19b. haematologica 2010; 95(2): 260-269

Biochem/physiol Actions

Givinostat (ITF2357) is a hydroxamate HDAC inhibitor that inhibits class I and class II enzymes. Givinostat posseses a very promising activity profile in multiple myeloma and acute myelogenous leukemia in vitro and in vivo. Givinostat also has anti-inflammatory activity and inhibits the secretion of the tumor necrosis factor-alpha (TNF-α), IL-1, and IL-6. Givinostat has been in multiple Phase 2 studies for both inflammatory diseases (Duchenne Muscular Dystrophy , Juvenile arthritis, Polycythemia Vera) and blood cancers (myelomas and lymphomas).

in vivo

target

HDAC

IC 50

hHDAC3: 157 nM (IC₅₀); hHDAC1: 198 nM (IC₅₀); hHDAC11: 292 nM (IC₅₀); hHDAC6: 315 nM (IC₅₀); hHDAC2: 325 nM (IC₅₀); hHDAC10: 340 nM (IC₅₀); hHDAC7: 524 nM (IC₅₀); hHDAC5: 532 nM (IC₅₀); hHDAC9: 541 nM (IC₅₀); hHDAC8: 854 nM (IC₅₀); hHDAC4: 1059 nM (IC₅₀); HD1-B: 7.5 nM (IC₅₀); HD1-A: 16 nM (IC₅₀); HD2: 10 nM (IC₅₀)