tcsc0511 Entinostat

Entinostat is the class I-selective HDAC inhibitor, with IC₅₀ of 243 nM, 453 nM, and 248 nM for HDAC1, HDAC2, and HDAC3.

IC50 & Target: IC50: 243 nM (HDAC1), 453 nM (HDAC2), 248 nM (HDAC3)^[1]

In Vitro: Binding affinity of Entinostat (MS-275) against HDAC1 and HDAC2 is 282 nM and 156 nM, respectively^[1]. Effects of the HDAC inhibitor Entinostat (MS-275) have been examined in human leukemia and lymphoma cells (U937, HL-60, K562, and Jurkat) as well as in primary acute myelogenous leukemia blasts in relation to differentiation and apoptosis. MS-275 displays dose-dependent effects in each of the cell lines. When administered at a low concentration (e.g., 1 μM), MS-275 exhibits potent antiproliferative activity, inducing p21CIP1/WAF1-mediated growth arrest and expression of differentiation markers (CD11b) in U937 cells. Entinostat (MS-275) potently induces cell death, triggering apoptosis in ~70% of cells at 48 h^[2].

In Vivo: Entinostat (MS-27-275) at 49 mg/kg shows marked antitumor effects against KB-3-1, 4-1St, and St-4 tumor lines, and a moderate effect against Capan-1 tumor. Entinostat at 24.5 mg/kg and 12.3 mg/kg also shows significant effects against these tumors. In addition, oral administration of Entinostat apparently increases the level of histone acetylation in HT-29 tumor xenografts 4-24 h after the administration^[3]. MS-275 administration (3.5 mg/kg i.p.) to Experimental autoimmune neuritis (EAN) rats once daily from the appearance of first neurological signs greatly reduces the severity and duration of EAN and attenuated local accumulation of macrophages, T cells and B cells, anddemyelination of sciatic nerves. Further, significant reduction of mRNA levels of pro-inflammatory interleukin-1β, interferon-γ, interleukine-17, inducible nitric oxide synthaseand matrix metalloproteinase-9 is observed in sciatic nerves of MS-275 treated EAN rats. In addition, MS-275 treatment increases proportion of infiltrated Foxp3⁺ cells and anti-inflammatory M2 macrophages in sciatic nerves of EAN rats^[4].