MGCD0103 AND PROTEASOME

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MGCD0103 AND PROTEASOME

Posted On : Jan-18-2012 | seen (359) times | Article Word Count : 584 |

INTRODUCTION

The epigenetic mechanism is involved in the transcription of different genes along with a vital role of HDACs (histone deacetylases). Histones proteins are attached with the DNA in the nucleus and are deacetylated as the acetyl group is dissociated from Lysine residues present in the core of these proteins due to the function of HDACs. This mechanism is very important for the cellular growth, proliferation, motility and apoptosis. Two main groups of HDACs are found, Zn2+ dependent and NAD+ dependent group. Among these groups one is further categorized in three forms. Cancer found in various organs like breast, stomach, colon and prostate are caused due to the histones (H4) deacetylation. And this action is done by these HDAC enzymes.MGCD0103 is one of the HDAC inhibitor was discovered during the chemical libraries screening; this is potent inhibitor against the cancer growth.

MGCD0103 also called as Mocetinostat is an analogue of deasmino. It is a derivative of benzamide and dihydrobromide salt. Different experimental research has proven that the specific targeted action on HDAC class is more effective cancer. The growth and cell proliferations mainly due to the activity of class I HDAC enzymes. Hence an efficient inhibitor of this class I HDAC enzymes are very effective in checking the growth of tumor and cancer cells. Like many other potent inhibitors (Entinostat, Droxinostat), MGCD0103 is an effective inhibitor of HDAC1 in human beings. During in-vitro studies it was also reported that this compound can also inhibit the action of HDAC2, 3 and 11.It has a constant effect for a long time period even on the removal of this inhibitor. These inhibitory characteristics of MGCD0103 lead to the cell cycle arrest and apoptosis of tumor cell lines; hence this is an apoptosis inhibitor. The over acetylation was noticed in the cancer cell lines when exposed to this inhibitor. MGCD0103 has broad spectrum effects on different cell lines when analyzed during in vitro conditions. However the in vivo action was also monitored in the xenograft models of cancer [1].

The pancreatic carcinoma cells were used in order to test the effects of MGCD0103 alone as well as in combination of gemcitabine. The cytotoxicity was enhanced significantly as a result of synergistic effects of both agents. The growth of tumors was inhibited in a greater extent. Hence this combination was proven to be very effective in order treat the pancreatic cancer cell lines as different vital genes were modulated [2]. Therefore this compound is also very efficient when used in combination of other anti-cancer chemical agents.

During various studies it was noticed that MGCD0103 was unable to arrest the growth of cells at G-1(GAP-1) phase. It inhibits the cell cycle at G-2 phase of the cell cycle. After 24 hour treatment most of the cells were killed due to some cytotoxic effects. This mechanism shows that the MGCD0103 have effects on the spindle fiber formation during mitosis. This was due to microtubules destabilization [3].

The aggresome function is inhibited due to the some HDAC inhibitors in HDAC-6 dependent manner. The TNF-α expression was also triggered by MGCD0103 and secreted in the HL cell lines. The cell death is promoted when combination of MGCD0103 and proteasome inhibitor was used and this did not depend on HDAC6 [4].

CONCLUSION

MGCD0103 is a broad spectrum inhibitor which stimulates cell cycle arrest at G-2 phase. It is also very effective with other apoptosis inhibitors and stimulates the death of cancerous cells and inhibits proliferation.

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<h1>MGCD0103 AND PROTEASOME </h1> Author: <a href='http://www.articleseen.com/profile_Dr.Rabia.aspx'>Dr.Rabia</a> INTRODUCTION

The epigenetic mechanism is involved in the transcription of different genes along with a vital role of HDACs (histone deacetylases). Histones proteins are attached with the DNA in the nucleus and are deacetylated as the acetyl group is dissociated from Lysine residues present in the core of these proteins due to the function of HDACs. This mechanism is very important for the cellular growth, proliferation, motility and apoptosis. Two main groups of HDACs are found, Zn2+ dependent and NAD+ dependent group. Among these groups one is further categorized in three forms. Cancer found in various organs like breast, stomach, colon and prostate are caused due to the histones (H4) deacetylation. And this action is done by these HDAC enzymes.MGCD0103 is one of the HDAC inhibitor was discovered during the chemical libraries screening; this is potent inhibitor against the cancer growth.

MGCD0103 also called as Mocetinostat is an analogue of deasmino. It is a derivative of benzamide and dihydrobromide salt. Different experimental research has proven that the specific targeted action on HDAC class is more effective cancer. The growth and cell proliferations mainly due to the activity of class I HDAC enzymes. Hence an efficient inhibitor of this class I HDAC enzymes are very effective in checking the growth of tumor and cancer cells. Like many other potent inhibitors (Entinostat, Droxinostat), MGCD0103 is an effective inhibitor of HDAC1 in human beings. During in-vitro studies it was also reported that this compound can also inhibit the action of HDAC2, 3 and 11.It has a constant effect for a long time period even on the removal of this inhibitor. These inhibitory characteristics of MGCD0103 lead to the cell cycle arrest and apoptosis of tumor cell lines; hence this is an apoptosis inhibitor. The over acetylation was noticed in the cancer cell lines when exposed to this inhibitor. MGCD0103 has broad spectrum effects on different cell lines when analyzed during in vitro conditions. However the in vivo action was also monitored in the xenograft models of cancer [1].

The pancreatic carcinoma cells were used in order to test the effects of MGCD0103 alone as well as in combination of gemcitabine. The cytotoxicity was enhanced significantly as a result of synergistic effects of both agents. The growth of tumors was inhibited in a greater extent. Hence this combination was proven to be very effective in order treat the pancreatic cancer cell lines as different vital genes were modulated [2]. Therefore this compound is also very efficient when used in combination of other anti-cancer chemical agents.

During various studies it was noticed that MGCD0103 was unable to arrest the growth of cells at G-1(GAP-1) phase. It inhibits the cell cycle at G-2 phase of the cell cycle. After 24 hour treatment most of the cells were killed due to some cytotoxic effects. This mechanism shows that the MGCD0103 have effects on the spindle fiber formation during mitosis. This was due to microtubules destabilization [3].

The aggresome function is inhibited due to the some HDAC inhibitors in HDAC-6 dependent manner. The TNF-α expression was also triggered by MGCD0103 and secreted in the HL cell lines. The cell death is promoted when combination of MGCD0103 and proteasome inhibitor was used and this did not depend on HDAC6 [4].

CONCLUSION

MGCD0103 is a broad spectrum inhibitor which stimulates cell cycle arrest at G-2 phase. It is also very effective with other apoptosis inhibitors and stimulates the death of cancerous cells and inhibits proliferation.

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We has established long-term and stable relationships with more than 10,000 customers from pharmaceutical and biotech companies, universities and research institutions. We have high quality inhibitors like KU-55933, 17-AAG, 17-DMAG & more.

Keywords : 17-DMAG, KU-55933,

Category : Health and Fitness : Health and Fitness

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