product name Pracinostat (SB939)
Description: Pracinostat, also known as SB939, is a potent and orally available inhibitor of histone deacetylase (HDAC) with a relatively stronger selectivity (more than 1000-fold) for class I, class II and class IV HDACs rather than class III HDACs. Pracinostat potently suppresses proliferation in a wide range of cancer cell lines, including colon cancer, ovarian cancer, prostate carcinomas, acute myeloid leukaemia (AML) and B cell lymphoma. SB939 induces the accumulation of acetylated histone H3 (AcH3) and acetylated α-tubulin and increases the expression of the cyclin dependent kinase inhibitor p21 in cancer cells.
References: Mol Cancer Ther. 2010 Mar;9(3):642-52; Br J Cancer. 2011 Mar 1;104(5):756-62.
358.48
Formula
C20H30N4O2
CAS No.
929016-96-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 72 mg/mL (200.8 mM)
Water: <1 mg/mL
Ethanol: 27 mg/mL (75.3 mM)
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425170
| In Vitro |
In vitro activity: SB939 has a 100-fold greater selectivity for HDACs than for Zn-binding non-HDAC enzymes, receptors, and ion channels. SB939 is a potent inhibitor of HDAC class I isoenzymes, HDAC1, HDAC2, HDAC3 and HDAC8 with the IC50 values ranging from 43 nM to 140 nM. SB939 inhibits HDAC class II isoenzymes , HDAC4, HDAC5, HDAC7, HDAC9 and HDAC10 significantly with the IC50 values ranging from 40 nM to 137 nM, with the exception of HDAC6 which shows IC50 of 1008 nM. It markedly inhibits HDAC11 of the HDAC class IV enzymes with IC50 of 93 nM, but shows no inhibitory activity against SIRT 1 of the class III HDACs. SB939 shows significant antiproliferative activity against a wide variety of tumor cell lines, especially Leukemia cells and cutaneous T-cell Lymphoma cells with IC50 values ranging from 50 nM (H9 cells) to 170 nM (HEL92.1.7 cells). Kinase 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. Cell Assay: Cells (HCT116, A2780, ACHN, MCF7, HL-60) 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. |
|---|---|
| In Vivo | Administration of SB939 (25 mg/kg to 100 mg/kg) displays a dose-dependent antitumor efficacy in a xenograft mice model of human colorectal cancer (HCT-116). This is approximately twice as efficacious as SAHA: SB939 causing a tumor growth inhibition of 94% versus 48% by SAHA with both at the maximum tolerated dose. Oral administration of SB939 at a dose of 50 mg/kg or 75 mg/kg in the APCmin genetic mice model of early-stage colon cancer markedly reduces the number of tumors , decreases cumulative hemocult scores and increases hematocrit values more effectively than 5-fluorouracil. |
| Animal model | BALB/c nude mice bearing HCT-116 human colon cancer xenografts, Male and APCmin mice |
| Formulation & Dosage | Dissolved in DMSO and prepared in 0.5% methylcellulose (w/v) and 0.1% Tween-80 in water; 25, 50, 75, or 100 mg/kg; Oral administration |
| References | Mol Cancer Ther. 2010 Mar;9(3):642-52; Br J Cancer. 2011 Mar 1;104(5):756-62. |
