LAQ824 (NVP-LAQ824,Dacinostat)是一种新型、高效的组蛋白去乙酰化酶（HDAC）抑制剂，IC50为32nM。
Cas No.:404951-53-7
Sample solution is provided at 25 µL, 10mM.
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LAQ824 (NVP-LAQ824,Dacinostat) is a novel, highly potent histone deacetylase (HDAC) inhibitor with an IC50 of 32nM[1]. By blocking HDAC activity, LAQ824 induces hyperacetylation of histones and up-regulates tumor-suppressor genes such as p21 and Rb, and promotes cell apoptosis[2]. LAQ824 is widely used in cancer epigenetics and anti-tumor mechanism studies[3][4].
In vitro, treatment of Daoy and D283 cells with LAQ824 (0.1µM for Daoy cells, 0.01µM for D283 cells) for 24 and 48h reduced cell viability, induced apoptosis, triggered G2/M arrest, and elevated acetylated histones H3/H4[5]. Treatment of 32D myeloid progenitor cells with LAQ824 (10-20nM; 7 days) suppressed cell proliferation, down-regulated c-Myc and BMI1 proteins, and abolished serial replating capacity[6].
In vivo, LAQ824 (1mg/kg; every 2 days for 9 weeks; i.p.) reduced high-fat-diet-induced obesity, adipose hypertrophy, hepatic steatosis and insulin resistance, and elevated body temperature and Ucp1/Ppargc1α expression in C57BL/6 male mice[7].
References:
[1] Catley L, Weisberg E, Tai YT, et al. NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003;102(7):2615-2622.
[2] Atadja P, Gao L, Kwon P, et al. Selective growth inhibition of tumor cells by a novel histone deacetylase inhibitor, NVP-LAQ824. Cancer Res. 2004;64(2):689-695.
[3] Mohseni J, Al-Najjar BO, Wahab HA, Zabidi-Hussin ZA, Sasongko TH. Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients. J Hum Genet. 2016;61(9):823-830.
[4] Ganai SA. Strategy for enhancing the therapeutic efficacy of histone deacetylase inhibitor dacinostat: the novel paradigm to tackle monotonous cancer chemoresistance. Arch Pharm Res. Published online October 19, 2015.
[5] Zhang S, Gong Z, Oladimeji PO, et al. A high-throughput screening identifies histone deacetylase inhibitors as therapeutic agents against medulloblastoma. Exp Hematol Oncol. 2019;8:30.
[6] Romanski A, Schwarz K, Keller M, et al. Deacetylase inhibitors modulate proliferation and self-renewal properties of leukemic stem and progenitor cells. Cell Cycle. 2012;11(17):3219-3226.
[7] Chu XY, Zhang CC, Zhang RX, Zhang JF, Xia B, Wu JW. Identification of Dacinostat as a potential anti-obesity compound through transcriptional activation of adipose thermogenesis in mice. Biochim Biophys Acta Mol Basis Dis. 2021;1867(9):166169.
LAQ824 (NVP-LAQ824,Dacinostat)是一种新型、高效的组蛋白去乙酰化酶（HDAC）抑制剂，IC50为32nM[1]。LAQ824通过阻断HDAC活性诱导组蛋白高乙酰化，上调p21和Rb等抑癌基因，并促进细胞凋亡[2]。LAQ824广泛用于癌症表观遗传学及抗肿瘤机制研究[3][4]。
体外实验中，用LAQ824处理Daoy和D283细胞（Daoy细胞0.1µM，D283细胞0.01µM；24和48小时）可降低细胞活性，诱导凋亡，引发G2/M期阻滞，并提高乙酰化组蛋白H3/H4水平[5]。用LAQ824（10-20nM；处理7天）处理32D髓系祖细胞，可抑制细胞增殖，下调c-Myc和BMI1蛋白表达，并完全消除其连续传代能力[6]。
体内实验中，LAQ824（1mg/kg；每2天一次，连续9周；腹腔注射）可减轻C57BL/6雄性小鼠高脂饮食诱导的肥胖、脂肪组织肥大、肝脏脂肪变性和胰岛素抵抗，并升高体温和Ucp1/Ppargc1α表达水平[7]。
| Cell experiment [1]: | |
Cell lines | human medulloblastoma cell lines Daoy and D283 |
Preparation Method | The human medulloblastoma cell lines Daoy and D283 were cultured in Eagle’s Minimum Essential Medium (MEM) containing 10% fetal bovine serum. Mycoplasma testing was conducted every 3 months to ensure no contamination. All cells were maintained in a humidified incubator at 37°C and 5% CO2. Cells were grown to 50-70% confluence and then treated with LAQ824 (0.1µM for Daoy cells, 0.01µM for D283 cells) for 24h and 48h. After incubation, floating and adherent cells were collected, washed with serum-free medium, and suspended in PBS. The cell suspension was stained with FITC-conjugated annexin V and propidium iodide (PI) using Cell Apoptosis Kit and then analyzed by flow cytometry. Cell apoptosis and cell cycle distribution analyses were performed using FlowJo. Viability was measured using the MTT Cell Proliferation Assay Kit. |
Reaction Conditions | 0.1µM for Daoy cells, 0.01µM for D283 cells; 24 and 48h |
Applications | LAQ824 reduced cell viability, induced apoptosis, and triggered G2/M arrest in Daoy and D283 cells. |
| Animal experiment [2]: | |
Animal models | male C57BL/6 mice |
Preparation Method | Six-week-old male C57BL/6 mice were acclimated for 2 weeks in the animal facility with free access to water and food (chow diet) under a 12h light/dark cycles at 22±2℃. At the age of 8 weeks, the mice were given high fat diet (HFD, 60% calories from fat) and randomly categorized into two groups. Each group consisted of two cages (three mice per cage). LAQ824 was dissolved in DMSO and then diluted 10 times in saline before given to mice by daily intraperitoneal administration (1mg/kg/2 days) for 9 weeks. After mice were sacrificed, the total mass of fat in different depots of the body (epididymal, inguinal, perirenal, subcutaneous, mesenteric, brown adipose tissue), and the mass of the gastrocnemius muscle, key internal organs including heart, liver, spleen, kidney, and lung were weighed. Plasma was taken from 6h fasted mice before sacrifice. The plasma biochemical parameters levels were measured using a Biochemical Analyzer. ELISA kit were used to assay plasma insulin. Glucose tolerance test (GTT) was performed following an overnight fast (16h) and the mice were given D-glucose (2g/kg body weight) by intraperitoneal injection. For insulin tolerance test (ITT), 6h fasted mice (from 6am to 12am) were given recombinant human insulin at the concentration of 1U/kg of body weight. Levels of plasma glucose from tail vein were measured at indicated time points (0, 30, 60, 90, and 120min) after injection. The body temperature was recorded by a rectal probe. Tissues of liver, BAT, iWAT, and eWAT were fixed in 4% paraformaldehyde for histological analysis. |
Dosage form | 1mg/kg; every 2 days for 9 weeks; i.p. |
Applications | LAQ824 reduced high-fat-diet-induced obesity, adipose hypertrophy, hepatic steatosis and insulin resistance, and elevated body temperature in C57BL/6 male mice. |
References: | |
| Cas No. | 404951-53-7 | SDF | |
| 别名 | 达诺司他,LAQ-824, NVP-LAQ 824 | ||
| 化学名 | (E)-N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide | ||
| Canonical SMILES | C1=CC=C2C(=C1)C(=CN2)CCN(CCO)CC3=CC=C(C=C3)C=CC(=O)NO | ||
| 分子式 | C22H25N3O3 | 分子量 | 379.46 |
| 溶解度 | ≥ 17.45 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6353 mL | 13.1766 mL | 26.3532 mL |
| 5 mM | 527.1 μL | 2.6353 mL | 5.2706 mL |
| 10 mM | 263.5 μL | 1.3177 mL | 2.6353 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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