Inhibition of Mdm2–MdmX RING–RING interaction by MMRi6 and its analog MMRi64.
A new class of small-molecule compounds has been discovered that are good candidates for novel targeted therapies in leukemia and lymphoma Rx. They drive cancer cells to suicide, RPCI researchers report. “We are excited about the unique activities of these compounds and will continue to focus our research efforts on development of their clinical potential,” says Xinjiang Wang, PhD. “These compounds kill cancer cells, not just stop cancer cell growth temporarily. These types of agents offer the promise of therapeutic benefit.”
They demonstrated that the small-molecule MMRi compounds have an advantage over p53-activating agents in current use as cancer therapies. MMRi compounds activate the pro-death function of the p53 pathway, whereas current p53-activating agents are effective in temporarily preventing cancer growth, but do not damage existing cancer cells or prevent cancer growth long-term. MMRi inhibits Mdm2-MdmX function, and eliminates the 2 cancer-causing proteins in cells – mechanisms potentially responsible for MMRi’s death-promoting effect in cancer. Dr. Wang and team report that MMRi64 is the first-in-class inhibitor of RING domain function of Mdm2-MdmX E3 ligase.
“This study opens a new area for anticancer drug development. MMRi compounds also can be used as a tool for better understanding the anti-death mechanisms developed by cancer cells,” continues Dr. Wang. “We are moving the research of MMRi compounds forward using both preclinical models and human cancer cell lines. Our hope is that further development of clinically useful MMRi will eventually provide a new treatment option for cancer patients.” https://www.roswellpark.org/media/news/study-identifies-new-class-anticancer-compounds-possible-targeted-therapy-blood-cancers
http://www.nature.com/cddis/journal/v6/n12/full/cddis2015358a.html
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