Mocetinostat (MGCD-0103)
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MedKoo CAT#: 201933

CAS#: 726169-73-9 (free base)

Description: Mocetinostat, also known as MGCD-0103, is a rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others.


Chemical Structure

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Mocetinostat (MGCD-0103)
CAS# 726169-73-9 (free base)

Theoretical Analysis

MedKoo Cat#: 201933
Name: Mocetinostat (MGCD-0103)
CAS#: 726169-73-9 (free base)
Chemical Formula: C23H20N6O
Exact Mass: 396.16986
Molecular Weight: 396.44
Elemental Analysis: C, 69.68; H, 5.08; N, 21.20; O, 4.04

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1.0g USD 650.0 Same Day
2.0g USD 1050.0 Same Day
5.0g USD 2250.0 Same Day
10.0g USD 3950.0 2 Weeks
20.0g USD 5950.0 2 Weeks
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Related CAS #: 726169-73-9 (free base)   944537-89-7 (HBr)  

Synonym: MGCD0103 ; MGCD 0103; MGCD-0103; Mocetinostat

IUPAC/Chemical Name: N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide

InChi Key: HRNLUBSXIHFDHP-UHFFFAOYSA-N

InChi Code: InChI=1S/C23H20N6O/c24-19-5-1-2-6-21(19)28-22(30)17-9-7-16(8-10-17)14-27-23-26-13-11-20(29-23)18-4-3-12-25-15-18/h1-13,15H,14,24H2,(H,28,30)(H,26,27,29)

SMILES Code: O=C(NC1=CC=CC=C1N)C2=CC=C(CNC3=NC=CC(C4=CC=CN=C4)=N3)C=C2

Appearance: White to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, DMF, and 1:1 DMF:PBS

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Biological target: Mocetinostat (MGCD0103) is an isotype-selective HDAC (Class I/IV) inhibitor with IC50s of 0.15, 0.29, 1.66 and 0.59 μM for HDAC1, HDAC2, HDAC3 and HDAC11, respectively.
In vitro activity: Treatment of SUM149 and HCC1937 cells with mocetinostat increased the acetylation of H3 lysine 9 (H3K9) and H3K27 in a dose-dependent manner (Figure 4A). Mocetinostat suppressed the proliferation of SUM149 and HCC1937 in MTT assays, with an IC50 value of 0.6 and 2.6 µM, respectively. In the presence of 0.5 µM mocetinostat, the colony formation was reduced by approximately 80% (P < 0.001) compared with the control cells (Figure 4B). To examine the effect of mocetinostat on cell cycle progression and apoptosis, this study performed flow cytometry of DNA content in SUM149 and HCC1937 cells. As shown in Figure 4C and 4D, mocetinostat treatment led to a substantial increase in G2/M phase and decreases in G1 and S phase cells, suggesting that it hinders cell-cycle progression, particularly in SUM149 cells. Mocetinostat also potently induced apoptosis in SUM149 and HCC1937 cells, as shown by Annexin V assay and western blot analysis of cleaved caspase-3 (Figure 4A and Supplementary Figure 5). Reference: Am J Cancer Res. 2017; 7(5): 1213–1226. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446485/
In vivo activity: MGCD (MGCD0103) treatment significantly inhibited the increase in blood glucose level (Fig. 1A), deformation of pancreatic islets, and infiltration of macrophages (Fig. 1C) in rats injected with a low dose (40 mg/kg) of STZ. In addition, MGCD infusion elevated the expression of SODs in the pancreas, and TEMPOL, an SOD mimetic, restored STZ-induced cell death (Fig. 5G) and activation of caspase-3 (Fig. 5H). These results indicate that MGCD protects the pancreas from the oxidative stress induced by the low dose of STZ through the expression of SODs. Reference: Biomed Pharmacother. 2019 Jan;109:921-929. https://pubmed.ncbi.nlm.nih.gov/30551546/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 49.67 125.29
DMF 25.0 63.06
DMF:PBS (pH 7.2) (1:1) 0.5 1.26

Preparing Stock Solutions

The following data is based on the product molecular weight 396.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Shan W, Jiang Y, Yu H, Huang Q, Liu L, Guo X, Li L, Mi Q, Zhang K, Yang Z. HDAC2 overexpression correlates with aggressive clinicopathological features and DNA-damage response pathway of breast cancer. Am J Cancer Res. 2017 May 1;7(5):1213-1226. PMID: 28560068; PMCID: PMC5446485. 2. Zhang Q, Sun M, Zhou S, Guo B. Class I HDAC inhibitor mocetinostat induces apoptosis by activation of miR-31 expression and suppression of E2F6. Cell Death Discov. 2016 Jun 6;2:16036. doi: 10.1038/cddiscovery.2016.36. PMID: 27551526; PMCID: PMC4979414. 3. Lee HA, Lee E, Do GY, Moon EK, Quan FS, Kim I. Histone deacetylase inhibitor MGCD0103 protects the pancreas from streptozotocin-induced oxidative stress and β-cell death. Biomed Pharmacother. 2019 Jan;109:921-929. doi: 10.1016/j.biopha.2018.10.163. Epub 2018 Nov 5. PMID: 30551546. 4. Huang HJ, Huang HY, Hsieh-Li HM. MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model. CNS Neurosci Ther. 2019 Feb;25(2):175-186. doi: 10.1111/cns.13029. Epub 2018 Jul 5. PMID: 29978554; PMCID: PMC6488906.
In vitro protocol: 1. Shan W, Jiang Y, Yu H, Huang Q, Liu L, Guo X, Li L, Mi Q, Zhang K, Yang Z. HDAC2 overexpression correlates with aggressive clinicopathological features and DNA-damage response pathway of breast cancer. Am J Cancer Res. 2017 May 1;7(5):1213-1226. PMID: 28560068; PMCID: PMC5446485. 2. Zhang Q, Sun M, Zhou S, Guo B. Class I HDAC inhibitor mocetinostat induces apoptosis by activation of miR-31 expression and suppression of E2F6. Cell Death Discov. 2016 Jun 6;2:16036. doi: 10.1038/cddiscovery.2016.36. PMID: 27551526; PMCID: PMC4979414.
In vivo protocol: 1. Lee HA, Lee E, Do GY, Moon EK, Quan FS, Kim I. Histone deacetylase inhibitor MGCD0103 protects the pancreas from streptozotocin-induced oxidative stress and β-cell death. Biomed Pharmacother. 2019 Jan;109:921-929. doi: 10.1016/j.biopha.2018.10.163. Epub 2018 Nov 5. PMID: 30551546. 2. Huang HJ, Huang HY, Hsieh-Li HM. MGCD0103, a selective histone deacetylase inhibitor, coameliorates oligomeric Aβ25-35 -induced anxiety and cognitive deficits in a mouse model. CNS Neurosci Ther. 2019 Feb;25(2):175-186. doi: 10.1111/cns.13029. Epub 2018 Jul 5. PMID: 29978554; PMCID: PMC6488906.

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1: Boumber Y, Younes A, Garcia-Manero G. Mocetinostat (MGCD0103): a review of an isotype-specific histone deacetylase inhibitor. Expert Opin Investig Drugs. 2011 Jun;20(6):823-9. doi: 10.1517/13543784.2011.577737. Epub 2011 May 10. Review. PubMed PMID: 21554162.

2: Sung V, Richard N, Brady H, Maier A, Kelter G, Heise C. Histone deacetylase inhibitor MGCD0103 synergizes with gemcitabine in human pancreatic cells. Cancer Sci. 2011 Jun;102(6):1201-7. doi: 10.1111/j.1349-7006.2011.01921.x. Epub 2011 Apr 18. PubMed PMID: 21375679.

3: Sikandar S, Dizon D, Shen X, Li Z, Besterman J, Lipkin SM. The class I HDAC inhibitor MGCD0103 induces cell cycle arrest and apoptosis in colon cancer initiating cells by upregulating Dickkopf-1 and non-canonical Wnt signaling. Oncotarget. 2010 Nov;1(7):596-605. PubMed PMID: 21317455; PubMed Central PMCID: PMC3093052.

4: Moreno-Bost A, Szmania S, Stone K, Garg T, Hoerring A, Szymonifka J, Shaughnessy J Jr, Barlogie B, Prentice HG, van Rhee F. Epigenetic modulation of MAGE-A3 antigen expression in multiple myeloma following treatment with the demethylation agent 5-azacitidine and the histone deacetlyase inhibitor MGCD0103. Cytotherapy. 2011 May;13(5):618-28. doi: 10.3109/14653249.2010.529893. Epub 2010 Dec 20. PubMed PMID: 21171821; PubMed Central PMCID: PMC3633222.

5: Buglio D, Mamidipudi V, Khaskhely NM, Brady H, Heise C, Besterman J, Martell RE, MacBeth K, Younes A. The class-I HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism. Br J Haematol. 2010 Nov;151(4):387-96. doi: 10.1111/j.1365-2141.2010.08342.x. Epub 2010 Sep 29. PubMed PMID: 20880107; PubMed Central PMCID: PMC3189488.

6: Chia K, Beamish H, Jafferi K, Gabrielli B. The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity. Mol Pharmacol. 2010 Sep;78(3):436-43. doi: 10.1124/mol.110.065169. Epub 2010 Jun 10. PubMed PMID: 20538840.

7: El-Khoury V, Moussay E, Janji B, Palissot V, Aouali N, Brons NH, Van Moer K, Pierson S, Van Dyck E, Berchem G. The histone deacetylase inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic leukemia cells through a mitochondria-mediated caspase activation cascade. Mol Cancer Ther. 2010 May;9(5):1349-60. doi: 10.1158/1535-7163.MCT-09-1000. Epub 2010 Apr 20. PubMed PMID: 20406947.

8: Blum KA, Advani A, Fernandez L, Van Der Jagt R, Brandwein J, Kambhampati S, Kassis J, Davis M, Bonfils C, Dubay M, Dumouchel J, Drouin M, Lucas DM, Martell RE, Byrd JC. Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia. Br J Haematol. 2009 Nov;147(4):507-14. doi: 10.1111/j.1365-2141.2009.07881.x. Epub 2009 Aug 31. PubMed PMID: 19747365; PubMed Central PMCID: PMC2779118.

9: Raeppel S, Zhou N, Gaudette F, Leit S, Paquin I, Larouche G, Moradei O, Fréchette S, Isakovic L, Delorme D, Fournel M, Kalita A, Lu A, Trachy-Bourget MC, Yan PT, Liu J, Rahil J, Wang J, Besterman JM, Murakami K, Li Z, Vaisburg A. SAR and biological evaluation of analogues of a small molecule histone deacetylase inhibitor N-(2-aminophenyl)-4-((4-(pyridin-3-yl)pyrimidin-2-ylamino)methyl)benzamide (MGCD0103). Bioorg Med Chem Lett. 2009 Feb 1;19(3):644-9. doi: 10.1016/j.bmcl.2008.12.048. Epub 2008 Dec 24. PubMed PMID: 19114304.

10: Le Tourneau C, Siu LL. Promising antitumor activity with MGCD0103, a novel isotype-selective histone deacetylase inhibitor. Expert Opin Investig Drugs. 2008 Aug;17(8):1247-54. doi: 10.1517/13543784.17.8.1247 . Review. PubMed PMID: 18616420.

11: Zhou N, Moradei O, Raeppel S, Leit S, Frechette S, Gaudette F, Paquin I, Bernstein N, Bouchain G, Vaisburg A, Jin Z, Gillespie J, Wang J, Fournel M, Yan PT, Trachy-Bourget MC, Kalita A, Lu A, Rahil J, MacLeod AR, Li Z, Besterman JM, Delorme D. Discovery of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide (MGCD0103), an orally active histone deacetylase inhibitor. J Med Chem. 2008 Jul 24;51(14):4072-5. doi: 10.1021/jm800251w. Epub 2008 Jun 21. PubMed PMID: 18570366.

12: Bonfils C, Kalita A, Dubay M, Siu LL, Carducci MA, Reid G, Martell RE, Besterman JM, Li Z. Evaluation of the pharmacodynamic effects of MGCD0103 from preclinical models to human using a novel HDAC enzyme assay. Clin Cancer Res. 2008 Jun 1;14(11):3441-9. doi: 10.1158/1078-0432.CCR-07-4427. PubMed PMID: 18519775; PubMed Central PMCID: PMC3444140.

13: Garcia-Manero G, Assouline S, Cortes J, Estrov Z, Kantarjian H, Yang H, Newsome WM, Miller WH Jr, Rousseau C, Kalita A, Bonfils C, Dubay M, Patterson TA, Li Z, Besterman JM, Reid G, Laille E, Martell RE, Minden M. Phase 1 study of the oral isotype specific histone deacetylase inhibitor MGCD0103 in leukemia. Blood. 2008 Aug 15;112(4):981-9. doi: 10.1182/blood-2007-10-115873. Epub 2008 May 21. PubMed PMID: 18495956.

14: Siu LL, Pili R, Duran I, Messersmith WA, Chen EX, Sullivan R, MacLean M, King S, Brown S, Reid GK, Li Z, Kalita AM, Laille EJ, Besterman JM, Martell RE, Carducci MA. Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors. J Clin Oncol. 2008 Apr 20;26(12):1940-7. doi: 10.1200/JCO.2007.14.5730. PubMed PMID: 18421048; PubMed Central PMCID: PMC3501257.

15: 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 Apr;7(4):759-68. doi: 10.1158/1535-7163.MCT-07-2026. PubMed PMID: 18413790.



Additional Information

Related CAS#
726169-73-9 (Mocetinostat)
944537-89-7 (Mocetinostat Dihydrobromide)