Cell lines

A549 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Reaction Conditions

50 μM, 16 hours

Applications

MGCD0103 showed dose-dependent inhibition of HDAC activity in whole cells. At high concentrations in A549 cells, MGCD0103 inhibited a maximum of 80% of total activity. Cells were then subsequently washed with drug-free media. The inhibitory activity of MGCD0103 was sustained at least 48 hours after drug removal followed by a slow reversal.

Animal models

Female CD-1 nude mice injected with A549 cells

Dosage form

Oral administration, 120 mg/kg

Applications

Administration of MGCD0103 (2HBr salt) significantly reduced growth of implanted advanced A549 tumors in nudemice in a dose-dependent manner after 13 days of daily administration. MGCD0103 (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blocked growth of tumors compared with vehicle treatment alone with no change in body weight. In addition, MGCD0103 did not reduce WBC counts and was well tolerated.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Mocetinostat, also known as MGCD0103 or MG0103, is an isotype-selective inhibitor of human histone deacetylases (HDAC), a family of enzymes involved in epigenetic regulation of gene transcription as well as cell proliferation, death and motility. Mocetinostat potently inhibits HDAC class I (HDAC1, HDAC2, and HDAC3) and class IV (HDAC11), with values of inhibition constant IC50 of 0.15 μmol/L, 0.29 μmol/L, 1.66 μmol/L, and 0.59 μmol/L respectively, rather than HDAC class II. Mocetinostat exerts anti-tumor activity against a broad range of human cancer cells through HDAC inhibition, in which it induces histone hyperacetylation and apoptosis and causes cell cycle blockade in a dose-dependent manner.

Reference

[1].Fournel M, Bonfils C, Hou Y, Yan PT, Trachy-Bourget MC, Kalita A, Liu J, Lu AH, Zhou NZ, Robert MF, Gillespie J, Wang JJ, Ste-Croix H, Rahil J, Lefebvre S, Moradei O, Delorme D, Macleod AR, Besterman JM, Li Z. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Mol Cancer Ther. 2008; 7(4): 759-768