Poster: Ex vivo activity of two novel dual topoisomerase
I and II inhibitors XR5944 and XR11576 against solid tumors
The original crystal structure of yeast topoisomerase
II, which is related to DNA gyrase and topoisomerase
IV, had suggested that this resistance-determining domain was not in proximity to the resistance-determining domains of GyrA and ParC (10); however, structures of other enzyme conformations suggested that the resistance-determining regions of both types of subunits might be in proximity during certain parts of the enzyme catalytic cycle, perhaps defining an enzyme conformation to which quinolones bind (11).
XR5000 acts as an inhibitor of both topoisomerases
I and II, enzymes which are critically involved in the replication of DNA during the process of cell division and which therefore play a key role in the proliferation of cancer cells.
The compounds target the bacterial enzyme topoisomerase
I and show promise as leads to develop into new antibacterial agents.
Zylka said that a temporary exposure to a topoisomerase
inhibitor in utero has the potential to have a long-lasting effect on the brain, by affecting critical periods of brain development.
Our study shows the magnitude of what can happen if topoisomerases
are impaired," said senior study author Mark Zylka, PhD, associate professor in the Neuroscience Center and the Department of Cell Biology and Physiology at UNC.
Evodiamine, a dual catalytic inhibitor of type 1 and 11 topoisomerases
, exhibits enhanced inhibition against camptothecin resistant cells.
We can test potential new drugs against topoisomerases
as well as help discover new inhibitors as a first step to developing brand new drugs.
Cozzarelli elucidated the nature of DNA architecture and growth through enzymologic studies of polymerases, ligases, recombinases, and topoisomerases
The QRDR within topoisomerases
contains hotspots for mutations around the active site, which are associated with raised MIC values for fluoroquinolones (10).
Cambridge, MA; 617-761-6996) and Xenova Group, plc (Slough, England; 44 (0) 1753 706600), have signed a license agreement for the development and North American commercialization of Xenova's novel compounds, which have a unique mechanism of action including dual inhibition of topoisomerases
I and II, for the treatment of solid tumors in cancer.
The callers in this nuclear dance hall are en- zymes called topoisomerases