【摘 要】
：
CDC25 phosphatases are key actors in cyclin-dependent kinases activation whose role is essential at various stages of the cell cycle.CDC25 expression is upregulated in a number of human cancers.CDC25
【机 构】
：
Discovery & Innovation Ipsen France
【出 处】
：
中国上海第七届国际新药发明科技年会
论文部分内容阅读
CDC25 phosphatases are key actors in cyclin-dependent kinases activation whose role is essential at various stages of the cell cycle.CDC25 expression is upregulated in a number of human cancers.CDC25 phosphatases are therefore thought to represent promising novel targets in cancer therapy.Here,we report the identification and the characterization of IRC-083864,an original bis-quinone moiety that is a potent and selective inhibitor of CDC25 phosphatases in the low nanomolar range.IRC-083864 inhibits cell proliferation of a number of cell lines,regardless of their resistance to other drugs.It irreversibly inhibits cell proliferation and cell cycle progression and prevents entry into mitosis.In addition,it inhibits the growth ofHCT-116 tumor spheroids with induction of p21 and apoptosis.Finally,IRC-083864 reduced tumor growth in mice with established human prostatic and pancreatic tumor xenografls.This study describes a novel compound,which merits further study as a potential anticancer agent.
其他文献
Effective tumor chemotherapy requires targeting the anticancer drug to tumor cells and its molecular sites of action.Systemic administration and non-targeted distribution of the drug within the living
Background During the past 10 years there has been growing interest in the role of mitochondrial dysfunction in many diseases,including heart disease,metabolic disorders,neurological diseases,and nutr
A large amount of experimental data on the effects of the nonsteroidal anti-inflammatory drugs (NSAIDs) on cyclooxygenase-1,2 (COX-1,2) have revealed a significant variability in IC50 and COX-1/COX-2
Drug transporters are membrane proteins involved in the uptake or efflux of drugs by several tissues such as the intestine,liver,kidney and brain.They can have a significant impact on the pharmacokine
Tremorgenic neuromycotoxicosis caused by extrolites from several Penicillium species (e.g.Penicillium crustosum) is an important syndrome in domestic animals.The potential hazard to humans remains unc
Cell lines are renewable and constitute an invaluable resource of central nervous system cell types for studies of news therapeutical agents against diseases of CNS.We have determined that flavonoids
For over three decades,controlled drug delivery by magnetic force,as exemplified by magnetic nanoparticles,has been of great interest,simply because it is relatively easy to apply a magnetic force ext
The main goal of the cancer research is to improve the clinical outcome of cancer patients.At present,we can perform tailor-made chemotherapy,the selection of effective chemotherapy based on evaluatio