货号：B7336

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

HDACs (Histone deacetylases) are a group of enzymes that remove acetyl groups and regulate the histone tail, protein-DNA interaction, chromatin conformation, and even transcription. There are 18 mammalian HDACs divided into four classes: class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10), class III (sirtuin family: sirt1-sirt7) and class IV (HDAC11). Belinostat, also called as PXD101, is a pan-HDAC inhibitor (IC50 = 27 nM, measured by HDAC enzymatic activity), inhibiting class I, II and IV HDAC isoforms with nanomolar potency. Like other HDAC pan inhibitors, the hyperacetylation of H3 and H4, which are the biomarkers for the inhibition of class I HDAC, can be observed in A2780 cells treated with 1 μM belinostat for various times (0.5 - 36h). Belinostat can inhibit the growth of a number of human tumor cell lines from various origins, including A2780, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852 cells, with IC50 ranging 0.2 - 3.4 μM. The induction of P21 and apoptosis, as determined with measurement of PARP cleavage, by belinostat can be observed after drug incubation for 24h with concentration <1 μM in these cell lines, except for PC3 and 2780AD cell line. Belinostat shows good pharmacokinetic and pharmacodynamic properties. Treatment of belinostat 10 - 40 mg/kg daily for a week can inhibit the tumor growth of A2780 tumor-bearing mice in a dose-dependent manner, along with the increase of acetylated histone H4. Co-administration of belinostat with bortezomib can synergistically induce cell death in CLL cells, which may due to the involving of other mechanism, like NF-kB inactivation and perturbation in the expression of proapoptotic and antiapoptotic proteins. Belinostat was approved for the treatment of patients with relapsed or refractory PTCL. Its clinical trial of treatment for solid tumors/hematological malignancies is undergoing. 

作用机制

The hydroxamic structure of belinostat can chelate the Zn ion of HDACs.

产品信息