Dacinostat (LAQ824)

製品コードS1095 バッチS109501

化学情報

	Synonyms	NVP-LAQ824	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₅N₃O₃
	分子量	379.459	CAS No.	404951-53-7
Solubility (25°C)*	体外	DMSO	76 mg/mL (200.28 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Dacinostat (LAQ824, NVP-LAQ824) is a novel HDAC inhibitor with IC50 of 32 nM and is known to activate the p21 promoter.
in vitro	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. ^[1] 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. ^[2]
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. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In Vitro Histone Deacetylase Assay
キナーゼアッセイ	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.
細胞アッセイ	細胞株	H1299, HCT116, DU145, PC3 and MDA435 cells
	濃度	0-10 μM
	反応時間	48 hours
	実験の流れ	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 X0, %Growth=(X-T₀)/T₀100; 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.
動物実験	動物モデル	HCT116 cells is injected s.c. into the right axillary (lateral) region of outbred athymic (nu/nu) female mice.
	投薬量	≤100 mg/kg
	投与方法	Administered via i.v.

参考

カスタマーフィードバック

: Data from [Diabetologia, 2012, 55(9), 2421-2431]

: Data from [Diabetologia, 2012, 55(9), 2421-31]

: Data from [Mol Pain, 2010, 6, 51]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Inhibition of Notch Signaling Enhances Antitumor Activity of Histone Deacetylase Inhibitor LAQ824 [ Int J Mol Sci, 2023, 24(17)13660]	PubMed: 37686467
Single-cell profiling-guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma [ Clin Transl Med, 2022, 12(5):e798]	PubMed: 35522945
Histone Deacetylase Inhibitors as a Therapeutic Strategy to Eliminate Neoplastic "Stromal" Cells from Giant Cell Tumors of Bone [ Cancers (Basel), 2022, 14(19)4708]	PubMed: 36230631
Continuous Activity Assay for HDAC11 Enabling Reevaluation of HDAC Inhibitors [ ACS Omega, 2019, 4(22):19895-19904]	PubMed: 31788622
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740]	PubMed: 30135193
[ Cell Death Dis, 2018, ]	PubMed: 29988031
Hippo signaling dysfunction induces cancer cell addiction to YAP [ Oncogene, 2018, 37(50):6414-6424]	PubMed: 30068939
Identification of novel multi-stage histone deacetylase (HDAC) inhibitors that impair Schistosoma mansoni viability and egg production [ Parasit Vectors, 2018, 11(1):668]	PubMed: 30587243
Measuring Histone Deacetylase Inhibition in the Brain [ Curr Protoc Pharmacol, 2018, 81(1):e41]	PubMed: 29927058
The WHHERE coactivator complex is required for retinoic acid-dependent regulation of embryonic symmetry. [ Nat Commun, 2017, 8(1):728]	PubMed: 28959017

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。