AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase

Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin.

Trichostatin A (TSA) and trapoxin (TPX) are potent inhibitors of histone deacetylases (HDACs). TSA is proposed to block the catalytic reaction by chelating a zinc ion in the active-site pocket through its hydroxamic acid group. On the other hand, the epoxyketone is suggested to be the functional group of TPX capable of alkylating the enzyme. We synthesized a novel TPX analogue containing a hydr...

NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma.

Histone deacetylase (HDAC) inhibitors are emerging as a promising new treatment strategy in hematologic malignancies. Here we show that NVP-LAQ824, a novel hydroxamic acid derivative, induces apoptosis at physiologically achievable concentrations (median inhibitory concentration [IC50] of 100 nM at 24 hours) in multiple myeloma (MM) cell lines resistant to conventional therapies. MM.1S myeloma ...

Synthesis and histone deacetylase inhibitory activity of new benzamide derivatives.

Newly synthesized benzamide derivatives were evaluated for their inhibitory activity against histone deacetylase. The structure of these derivatives was unrelated to the known inhibitors, and IC(50) values of the active compounds were in the range of 2-50 microM. Structure-activity relationship on the benzanilide moiety showed that the 2'-substituent, an amino or hydroxy group, was indispensabl...

Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against human endometrial cancer cells.

BACKGROUND Histone deacetylase inhibitors (HDACIs) can inhibit cell proliferation, induce cell cycle arrest and stimulate apoptosis of cancer cells. MATERIALS AND METHODS The effects of a novel HDACI, MS-275, on 4 endometrial cancer cell lines and normal human endometrial epithelial cells was investigated. Endometrial cancer cells were treated with various concentrations of MS-275 and its eff...

a structure–activity relationship survey of histone deacetylase (hdac) inhibitors