product name LAQ824
Description: LAQ824, also known as Dacinostat, is a hydroxamate histone deacetylase inhibitor with potential anticancer activity. LAQ824 sensitized nonsmall cell lung cancer to the cytotoxic effects of ionizing radiation. LAQ824 reduced clonogenic survival of the H23 and H460 cell lines five-fold compared with controls and four-fold compared with either agent alone (P<0.001). In phase I trials, LAQ824 was well tolerated at doses that induced accumulation of histone acetylation, with higher doses inducing changes consistent with HSP90 inhibition.
References: Cancer Res. 2004 Jan 15;64(2):689-95; J Immunol. 2011 Apr 1;186(7):3986-96.
379.46
Formula
C22H25N3O3
CAS No.
404951-53-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 76 mg/mL (200.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL
Synonyms
NVP-LAQ824
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19425181
| In Vitro |
In vitro activity: LAQ824 activates the expression of the gene encoding the p21 cell cycle inhibitor by activating the p21 promoter with 50% of the maximal promoter activation (AC50) of 0.30 μM. LAQ824 inhibits the cell growth of both H1299, a non-small cell lung carcinoma line, and HCT116, a colon cancer cell line with IC50 of 0.15 μM and 0.01 μM, respectively, and the antiproliferative effect of LAQ824 is selective toward the tumor cell lines while inducing only growth arrest in normal fibroblasts. Furthermore, LAQ824 induces a dose-dependent increase of p21 protein in A549 cells and an increase in the hypophosphorylated state of the Rb tumor suppressor. A recent study shows that LAQ824 induces chromatin changes at the level of the IL-10 gene promoter that lead to enhanced recruitment of the transcriptional repressors HDAC11 and PU.1 and inhibits IL-10 production in BALB/c murine macrophages. Kinase Assay: HDAC enzymes are partially purified from H1299 cell lysate by ion exchange chromatography using the Q Sepharose Fast Flow column. Enzyme complexes are collected from 500 mg of total cell lysate by immunoprecipitation with cdk2 polyclonal antibody or cdk1/cdc2 monoclonal antibody. Immunoprecipitates are resuspended in kinase buffer (50 mM Hepes, pH 8, 10 mM MgCl2, 2.5 mM EDTA, 1 mM dithiothreitol, 20 mM ATP, 10 mM β-glycerophosphate, 0.1 mM NaVO4, 1 mM sodium fluoride, 50 mM ATP, 10 μCi of [γ-32P]ATP) along with 1 μg of pRb recombinant protein substrate (cdk2) or 10 mL of H1 histone mixture containing 20 μg of substrate (cdc2). Phosphorylated Rb and H1 histone are resolved by electrophoresis and quantitated using a PhosphorImager. Cell Assay: Cell proliferation is measured using an adaptation of published procedures (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfonyl)-2H-tetrazolium assay). The cells are seeded in 12-well dishes and cultured in RPMI 1640 containing 10% FBS. The cells are cultured in the presence of various concentrations of TSA (up to 1,000 ng/mL). To examine the growth inhibition by TSA, viable cell numbers are determined by trypan blue dye exclusion, counted in a Nesbauer-type hemocytometer for 0 hour, 24 hours, and 48 hours. The same amount of ethanol is added to the RPMI 1640 medium as the control experiment. All experiments are performed in duplicate and repeated 3 times The average background value (treatment with medium alone) is subtracted from each experimental well; triplicate values are averaged for each compound dilution. The following formulas are used to calculate the percentage of growth: If X<t0, %Growth=(X-T0)/T0*100; If X>T0, %Growth=(X-T0)/(GC-T0)*100. where T0 is the average value of T0 − background, GC is the average value of untreated cells (in triplicate) − background, and X is the average value of compound-treated cells (in triplicate)-background. The “% Growth” is plotted against compound concentration and used to calculate the IC50 using the linear regression techniques between data points to predict the concentration of compounds at 50% inhibition. |
|---|---|
| In Vivo | In HCT116 and human colon tumor xenografts in nude mice, LAQ824 treatment at 100 mg/kg produces the inhibitory effects on tumor growth in a dose-dependent mode without general cytotoxicity. |
| Animal model | HCT116 cells is injected s.c. into the right axillary (lateral) region of outbred athymic (nu/nu) female mice. |
| Formulation & Dosage | Dissolved in DMSO; ≤100 mg/kg; i.v. administration. |
| References | Cancer Res. 2004 Jan 15;64(2):689-95; J Immunol. 2011 Apr 1;186(7):3986-96. |
