Entinostat (MS-275)

HDAC3, HDAC1

376, 41

A2780, HT-29, HTC-15, KB-3-1, 4-1St, St-4, Capan-1 and Calu-3 cells are injected subcutaneously into the flank of nude mice.

MS-275 is currently in Phase I/II clinical trials in recurrent advanced non-small cell lung cancer, combining with 5-azacytidine.

12.3, 24.5 and 49 mg/kg

0.51 M, 0.51 M, 0.51 M, 0.51 M, 0.51 M, 0.51 M

MS-275 exhibits great antitumor activity against human tumor xenografts except HCT-15 at 49 mg/kg. [1] MS-275 demonstrates promising therapeutic potential in both solid and hematologic malignancies, as well as regulation of physiologic and aberrant gene expression. [4] MS-275, combination with IL-2, has great antitumor activity to renal cell carcinoma xenograft model, which due to decreased T regulatory cells and increased splenocytes. [5]

[6], Standard HDAC Assays, Rat liver enzyme is diluted 1:6 with HDAC buffer. Recombinant human HDACs are diluted 1:4 in HDAC buffer. For standard HDAC assays, 60 uL of HDAC buffer is mixed with 10 uL of diluted enzyme solution at 30 C. The HDAC reaction is started by adding 30 uL substrate solution in HDAC buffer followed by 30 min of incubation at 30 C. The reaction is stopped by adding 100 uL trypsin solutions (10 mg/ml trypsin in 50 mM Tris-HCl [pH 8.0], 100 mM NaCl, 2 uM TSA). After a 20 min incubation period at 30 C, the release of AMC is monitored by measuring the fluorescence at 460 nm (lambdaex = 390 nm). Fluorescence intensity is calibrated using free AMC. For standard time course experiments, 20 pmol of substrate is used in the initial 100 uL HDAC reaction. Km and Vmax values are determined by measuring the fluorescence AMC generated by enzymatic cleavage of 2–50 pmol of substrate. The experimental data are analyzed using a Hanes plot. The AMC signals are recorded against a blank with buffer andubstrate but without the enzyme.

DMSO 75 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL

pyridin-3-ylmethyl 4-((2-aminophenyl)carbamoyl)benzylcarbamate