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]。