Pracinostat (SB939) is a novel HDAC inhibitor with improved in vivo properties compared to other HDAC inhibitors currently in Clinicalal trials, allowing oral dosing. Data demonstrate that Pracinostat is a potent and effective anti-tumor drug with potential as an oral therapy for a variety of human hematological and solid tumors.

HDAC3:43 nM, HDAC5:47 nM, HDAC10:40 nM, HDAC1:49 nM, HDAC4:56 nM

50 mg/kg SB939选择性刺激CT-116移植瘤组织生长.SB939对SAHA的肿瘤生长抑制率为94％.SB939作用于裸鼠,比SAHA具有更强的药物动力学效果和口服生物有效性.SB939抑制APCmin鼠腺瘤形成和提高血球密度,效果比5-氟尿嘧啶好.SB939作用于肿瘤模型(HCT-116,PC-3,A2780,MV4-11,Ramos),具有抗癌活性和高效性.

SB939对HDAC的选择性比锌结合的非HDAC酶、受体和离子通道高100倍。SB939可显著抑制HDAC II类同工酶,HDAC4,HDAC5,HDAC7,HDAC9和HDAC10,IC50值范围为40 nM至137 nM,对HDAC6无此作用,其显示的IC50为1008 nM。它显著抑制HDAC IV类酶的HDAC11,IC50为93 nM,但对III类HDACs的SIRT1没有抑制活性。SB939对各种肿瘤细胞系,尤其是白血病细胞和皮肤T细胞淋巴瘤细胞显示出显著的抗增殖活性,IC50值范围从50 nM（H9细胞）至170 nM（HEL92.1.7细胞）。

HDAC enzyme assay: All recombinant HDAC enzymes, with the exception of SIRT1, are cloned and expressed in S*BIO. The reaction mix containing 2.5 or 5 μL of the HDAC isoenzyme, assay buffer (25 mM Tris-HCl, pH 7.5; 137 mM NaCl; 2.7 mM KCl, 1 mM MgCl2 and 1 mg/mL BSA), different concentrations of SB939, and the fluorogenic deacetylase substrate Flour de LysTM in a total reaction volume of 33 μL is incubated at room temperature for 2 hours. 16 μL of Flour de LysTM developer is added and incubated for an additional 10 minutes. The emitted light is measured at 460 nm in a microplate reader. IC50 values are generated using the XLfit software.

Cells are seeded in 96-well plates in the log growth phase at a predetermined optimal density, and rested for 24 hours (adherent cells) or 2 hours (suspension cells), respectively. They are exposed to different concentrations of SB939 for 96 hours. Cell proliferation assays are done using either the CyQUANT cell proliferation assay kit for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit for suspension cells.(Only for Reference)