product name HPOB
Description: HPOB is a potent, selective HDAC6 inhibitor with IC50 of 56 nM, >30-fold selectivity over other HDACs. In normal HFS and transformed LNCaP cells, HPOB inhibited cell growth but not viability, induced acetylation of α-Tubulin, but not histones. HPOB enhanced etoposide-, doxorubicin-, and SAHA-induced cell death in transformed cell but not in normal cell. HPOB enhanced the effectives of anticancer drugs via apoptotic pathway and activated DNA damage response in transformed cell.
References: Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15704-9.
314.34
Formula
C17H18N2O4
CAS No.
1429651-50-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 62 mg/mL (197.2 mM)
Water: <1 mg/mL
Ethanol: 38 mg/mL warmed (120.9mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19424459
| In Vitro |
In vitro activity: In normal (HFS) and transformed (LNCaP, A549, and U87) cells, HPOB induces acetylation of α-tubulin, however, not histones, and inhibits cell growth, however, not viability. In HFS cells, HPOB enhances transformed cell death induced by etoposide, doxorubicin, or SAHA. HPOB also enhancing etoposide-induced transformed cell death via the apoptotic pathway in transformed cells. Kinase Assay: In vitro activities of the 11 recombinant human zinc-dependent HDAC enzymes are detected by fluorigenic release of 7-amino-4-methylcoumarin from substrate upon deacetylase enzymatic activity. A series of dilutions of the unique HDAC6 compound, tubacin, and SAHA are prepared with 10% DMSO in HDAC assay buffer, and 5 μL of the dilution was added to a 50-μL reaction so that the final concentration of DMSO is 1% in all of the reactions. The enzymatic reactions are conducted in duplicate at 37 °C for 30 min in a 50-μL mixture containing HDAC assay buffer, 5 μg BSA, an HDAC substrate, an HDAC enzyme, and a test compound. After enzymatic reactions, 50 μL of 2× HDAC developer is added to each well, and the plate is incubated at room temperature for an additional 15 min. Fluorescence intensity is measured at an excitation of 360 nm and an emission of 460 nm using a Synergy microplate reader. Negative (no enzyme, no inhibitor, a drug with no HDAC inhibition activity) and positive controls (known HDAC inhibitor SAHA) are included in the assays. IC50 is determined at the drug concentration that results in 50% reduction of HDAC activity compared with the control. Cell Assay: Normal (HFS) and transformed (LNCaP, A549, and U87) cells are cultured with indicated doses of HPOB for 72 h. Five micromolars SAHA is a positive control.Graphs were constructed using Prism 5. |
|---|---|
| In Vivo | In mice bearing CWR22 human prostate cancer xenografts, HPOB (300 mg/kg/d i.p.), when in combination with SAHA, causes suppression of the growth of established tumors, while produces no significant suppression when used alone. |
| Animal model | Mice bearing CWR22 human prostate cancer xenografts |
| Formulation & Dosage | Dissolved in DMSO; 300 mg/kg daily; i.p. injection. |
| References | Proc Natl Acad Sci U S A. 2013 Sep 24;110(39):15704-9. |
