A4089-5mg | Mocetinostat (MGCD0103, MG0103) [726169-73-9] Clinisciences

Background

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

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

Product Citation

1. Aran Merati, Spandana Kotian, et al. "Glioma Stem Cells Are Sensitized to BCL-2 Family Inhibition by Compromising Histone Deacetylases." Int J Mol Sci. 2023 Sep 5;24(18):13688. PMID: 37761989
2. Spandana Kotian, Rachel M Carnes, et al. "Enhancing Transcriptional Reprogramming of Mesenchymal Glioblastoma with Grainyhead-like 2 and HDAC Inhibitors Leads to Apoptosis and Cell-Cycle Dysregulation." Genes (Basel). 2023 Sep 12;14(9):1787. PMID: 37761927
3. Topper MJ, Vaz M, et al. "Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer." Cell. 2017 Nov 30;171(6):1284-1300.e21. PMID:29195073
4. Bagnall NH, Hines BM, et al. "Insecticidal activities of histone deacetylase inhibitors against a dipteran parasite of sheep, Lucilia cuprina." Int J Parasitol Drugs Drug Resist. 2017 Apr;7(1):51-60. PMID:28110187

Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	396.44
Cas No.	726169-73-9
Formula	C₂₃H₂₀N₆O
Synonyms	MGCD-0103
Solubility	insoluble in EtOH; insoluble in H2O; ≥19.8 mg/mL in DMSO
Chemical Name	N-(2-aminophenyl)-4-[[(4-pyridin-3-ylpyrimidin-2-yl)amino]methyl]benzamide
SDF	Download SDF
Canonical SMILES	C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC3=NC=CC(=N3)C4=CN=CC=C4
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]
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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C 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 experiment: [1]
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.
References: [1] Fournel M, Bonfils C, Hou Y, et al. MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo. Molecular Cancer Therapeutics, 2008, 7(4): 759-768.

Biological Activity

Description	Mocetinostat (MGCD0103) is a potent inhibitor of HDAC with most potency for HDAC1 with IC50 of 0.15 μM, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8.
Targets	HDAC1	HDAC2	HDAC3
IC50	0.15 μM	0.29 μM	1.66 μM