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SB939 is a novel potent and orally active histone deacetylase with high tumor exposure and efficacy in mouse models of colorectal cancer. The IC50 value for HDAC1 is 52 nM. In vitro, SB939 inhibits class I, II and IV HDACs, with no effects on other zinc binding enzymes, and shows significant antiproliferative activity against a wide variety of tumor cell lines. It has very favorable pharmacokinetic properties after oral dosing in mice, with >4-fold increased bioavailability and 3.3-fold increased half-life over suberoylanilide hydroxamic acid (SAHA).
Patent. WO2025229179A1 2025 Nov 06; .
Patent. WO2025229179A1
SB939 purchased from AbMole
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Source | Mol Cancer Ther (2010). Figure 1. SB939 |
| Method | Western blots | |
| Cell Lines | HCT-116 colon cancer cells | |
| Concentrations | 0.25 to 1 μmol/L | |
| Incubation Time | 24 h | |
| Results | No signal for acH3 could be detected in vehicle-treated cells, whereas SB939 in concentrations of 0.125 μmol/L and above induced acH3 and the acetylation of α-tubulin after 24 h of treatment. Concentrations of 0.25 μmol/L and above led to decreased retinoblastoma serine phosphorylation on S807/811, an increase of the cyclin-dependant kinase inhibitor p21Cip/WAF. |
| Cell Experiment | |
|---|---|
| Cell lines | Colo205, HCT-116, A2780, PC3, DU145, MCF7, NCI-H460, HEP3B cells line |
| Preparation method | Cell Proliferation Assay Cells were seeded in 96-well plates at a predetermined optimal density, in the log growth phase, and rested for 24 h (adherent cells) or 2 h (suspension cells), respectively, before treatment with SB939. All experiments were done in triplicates for 96 h, with 1% solvent, using either the CyQUANT Cell proliferation assay kit (Invitrogen Corp.) for adherent cells or the CellTiter96 Aqueous One solution cell proliferation kit (Promega Corp.) for suspension cells, according to the manufacturer's instructions, in a total volume of 100 μL with SB939 concentrations from 100 μmol/L to 1.5 nmol/L in nine serial dilution steps. IC50 were determined using the XLfit software (IDBS). |
| Concentrations | 0~100 μ M |
| Incubation time | 96 h |
| Animal Experiment | |
|---|---|
| Animal models | HCT-116 Xenograft Mouse Model(Female BALB/c nude mice) |
| Formulation | 0.5% methylcellulose (w/v) and 0.1% Tween-80 in water (oral) or normal saline(i.v) |
| Dosages | once daily for 21 d with 25, 50, 75, or 100 mg/kg |
| Administration | oral |
| Molecular Weight | 358.48 |
| Formula | C20H30N4O2 |
| CAS Number | 929016-96-6 |
| Solubility (25°C) | DMSO 65 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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