mi-219 and Neoplasms

mi-219 has been researched along with Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for mi-219 and Neoplasms

Article	Year
Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition. Proceedings of the National Academy of Sciences of the United States of America, 2008, Mar-11, Volume: 105, Issue:10 We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2-p53 interaction. MI-219 binds to human MDM2 with a K(i) value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2-p53 interaction and activates the p53 pathway in cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment. Topics: Administration, Oral; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Humans; Indoles; Mice; Models, Molecular; Neoplasms; Protein Binding; Proto-Oncogene Proteins c-mdm2; Spiro Compounds; Time Factors; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays	2008

Article

Year

Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition.

Proceedings of the National Academy of Sciences of the United States of America, 2008, Mar-11, Volume: 105, Issue:10

We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2-p53 interaction. MI-219 binds to human MDM2 with a K(i) value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2-p53 interaction and activates the p53 pathway in cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Humans; Indoles; Mice; Models, Molecular; Neoplasms; Protein Binding; Proto-Oncogene Proteins c-mdm2; Spiro Compounds; Time Factors; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays

2008