Kinases as Druggable Targets in Trypanosomatid Protozoan Parasites
نویسندگان
چکیده
Parasites Christopher Merritt,‡ Lisseth E. Silva,† Angela L. Tanner,† Kenneth Stuart,‡ and Michael P. Pollastri*,† †Department of Chemistry & Chemical Biology, Northeastern University, 417 Egan Research Center, 360 Huntington Avenue, Boston, Massachusetts 02115, United States ‡Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, Washington 98109-5219, United States
منابع مشابه
2,4-Diaminopyrimidines as Potent Inhibitors of Trypanosoma brucei and Identification of Molecular Targets by a Chemical Proteomics Approach
BACKGROUND There is an urgent need to develop new, safe and effective treatments for human African trypanosomiasis (HAT) because current drugs have extremely poor safety profiles and are difficult to administer. Here we report the discovery of 2,4-diaminopyrimidines, exemplified by 4-[4-amino-5-(2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-carboxylic acid phenylamide (SCYX-5070), as pot...
متن کاملThe Susceptibility of Trypanosomatid Pathogens to PI3/mTOR Kinase Inhibitors Affords a New Opportunity for Drug Repurposing
BACKGROUND Target repurposing utilizes knowledge of "druggable" targets obtained in one organism and exploits this information to pursue new potential drug targets in other organisms. Here we describe such studies to evaluate whether inhibitors targeting the kinase domain of the mammalian Target of Rapamycin (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the kinetoplas...
متن کاملTrypanosomatid comparative genomics: Contributions to the study of parasite biology and different parasitic diseases
In 2005, draft sequences of the genomes of Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, also known as the Tri-Tryp genomes, were published. These protozoan parasites are the causative agents of three distinct insect-borne diseases, namely sleeping sickness, Chagas disease and leishmaniasis, all with a worldwide distribution. Despite the large estimated evolutionary distance among...
متن کاملConservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites.
Endonuclease G is a mitochondrial protein implicated in DNA fragmentation during apoptosis in cell types ranging from fungi to mammals. Features of programmed cell death have been reported in a number of single-celled organisms, including the human trypanosomatid parasites Leishmania and Trypanosoma. However, the protozoan cell death pathways and the effector molecules involved in such processe...
متن کاملProgrammed cell death in trypanosomatids: is it an altruistic mechanism for survival of the fittest?
The protozoan parasites Leishmania, Trypanosoma cruzi and Trypanosoma brucei show multiple features consistent with a form of programmed cell death (PCD). Despite some similarities with apoptosis of mammalian cells, PCD in trypanosomatid protozoans appears to be significantly different. In these unicellular organisms, PCD could represent an altruistic mechanism for the selection of cells, from ...
متن کامل