ITF2357 - HDAC Inhibitor

ITF2357 is a new synthetic inhibitor of class I and II histone deacetylases (HDAC) with a potent anti-proliferative and pro-apoptotic activity against several hematologic malignancies both in vitro and in vivo.

IUPAC Name:
{6-[(diethylamino)methyl]-2-naphthyl}methyl {4-[(hydroxyamino)carbonyl]phenyl}carbamate
Molecular Weight: 421,50 g/mol
Molecular Formula: C24H27N3O4
SMILES: CCN(CC)Cc3cc1ccc(cc1cc3)COC(=O)Nc2ccc(C(=O)NO)cc2
Canonical SMILES: CCN(CC)Cc1ccc2cc(COC(=O)Nc3ccc(cc3)C(=O)NO)ccc2c1
InChIKey Identifier: YALNUENQHAQXEA-UHFFFAOYSA-N
CAS Number: n/a
Melting point: n/a °C
Solubility: soluble in DMSO
2D Molfile: Get the molfile
Synonyms: n/a

ITF2357 induces apoptosis of multiple myeloma (MM) and acute myelogenous leukemia (AML) cells and this apoptosis takes place following induction of p21 and down-modulation of Bcl-2 and Mcl-1 proteins.

ITF2357 is 2-10-fold more potent than vorinostat. It has been reported in one preclinical study comparing the cytotoxic effects of ITF2357 versus vorinostat in human myeloma cell lines and freshly isolated MM samples.

References:
1) Rambaldi A, et al. The new histone deacetylase inhibitor ITF2357 is a strong inducer of apoptosis in multiple myeloma cells. Presented at the 10th Congress of the European Hematology Association, Stockholm, Sweden, June 2-5, 2005. Abstract 0230.
2) Pathil et al. HDAC Inhibitor Treatment of Hepatoma Cells Induces Both TRAIL-Independent Apoptosis and Restoration of Sensitivity to TRAIL. Hepatology, Vol. 43, No. 3, 2006.
3) Galli et al. A phase II multiple dose clinical trial of histone deacetylase inhibitor ITF2357 in patients with relapsed or progressive multiple myeloma. Ann Hematol (2010) 89:185–190.