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Found 193 documents (0.001 sec)   1 - 10 / 193  >  >> Rows
Novel Compound Series to Treat African Trypanosomiasis 
Novel compound series of phosphofructokinase allosteric inhibitors which show excellent efficacy in vitro against the parasite and in mouse models of the disease in vivo. Only a short treatment time is required as those compounds kill the parasite faster than any reported so far. The inhibitors are safe and show favourable pharmacokinetic properties including oral bioavailability and ability to cross the blood brain barrier. The well characterised inhibitors of this novel trypanosomiasis target have the potential to fill the unmet need for safe, cheap, easily administered drugs with short course for treatment for African trypanosomiasis. OPPORTUNITY African Trypanosomiasis is a neglected tropical disease caused by 2 subspecies Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It develops in 2 distinct stages with the 1st, body stage, resulting in cold-like symptoms and the 2nd, central nervous system stage, characterised by severe neurological symptoms. It is fatal if left untreated. It is most prevalent in economically disadvantaged rural communities in Africa which have little health infrastructure. Existing treatments are only available intravenously or are subspecies specific. Moreover, they often have severe side effects, long treatment duration, drug resistance and are expensive. There is therefore an urgent need for new effective and easily administered drugs. TECHNOLOGY OVERVIEW Phosphofructokinase (PFK) is an enzyme in the glycolytic pathway which converts fructose 6-monophosphate to fructose 1, 6-biphosphate on the cascade of converting glucose to pyruvate and ATP. Glycolysis is the sole source of ATP for the bloodstream form of the parasite and blocking it has been shown to kill the parasite much faster than any other drug mechanism. These compounds target the allosteric binding site on the parasite PFK which locks the enzyme in an inactive state. This allosteric pocket is unique to parasite PFK, therefore human phosphofructokinase is completely unaffected by the compounds minimising side effects. The drugs have been extensively characterised both in vitro and in vivo in terms of selectivity, potency and pharmacokinetics and show very favourable properties. Moreover, Trypanosoma brucei's phosphofructokinase enzyme - compounds interaction have been very well studied by numerous crystal structures which would allow them to be easily modified to further improve properties. BENEFITS  Novel validated target, well characterised mechanism of action and excellent structure-activity relationship  Compounds effective against both subspecies of the parasite and both stages of the disease  Orally bioavailable and able to cross the blood brain barrier in favourable proportions  Safe and effective in a mouse model with very short treatment duration (1-2 days)  Very fast time to completely kill the parasite (minutes vs days for other drug classes)  Can be used in combination with current medicines as they have a different mechanism of action
Submission ID: 3161,  Publication date: 2018-05-17
Novel Compound Series to Treat African Trypanosomiasis 
Novel compound series of phosphofructokinase allosteric inhibitors which show excellent efficacy in vitro against the parasite and in mouse models of the disease in vivo. Only a short treatment time is required as those compounds kill the parasite faster than any reported so far. The inhibitors are safe and show favourable pharmacokinetic properties including oral bioavailability and ability to cross the blood brain barrier. The well characterised inhibitors of this novel trypanosomiasis target have the potential to fill the unmet need for safe, cheap, easily administered drugs with short course for treatment for African trypanosomiasis. OPPORTUNITY African Trypanosomiasis is a neglected tropical disease caused by 2 subspecies Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It develops in 2 distinct stages with the 1st, body stage, resulting in cold-like symptoms and the 2nd, central nervous system stage, characterised by severe neurological symptoms. It is fatal if left untreated. It is most prevalent in economically disadvantaged rural communities in Africa which have little health infrastructure. Existing treatments are only available intravenously or are subspecies specific. Moreover, they often have severe side effects, long treatment duration, drug resistance and are expensive. There is therefore an urgent need for new effective and easily administered drugs. TECHNOLOGY OVERVIEW Phosphofructokinase (PFK) is an enzyme in the glycolytic pathway which converts fructose 6-monophosphate to fructose 1, 6-biphosphate on the cascade of converting glucose to pyruvate and ATP. Glycolysis is the sole source of ATP for the bloodstream form of the parasite and blocking it has been shown to kill the parasite much faster than any other drug mechanism. These compounds target the allosteric binding site on the parasite PFK which locks the enzyme in an inactive state. This allosteric pocket is unique to parasite PFK, therefore human phosphofructokinase is completely unaffected by the compounds minimising side effects. The drugs have been extensively characterised both in vitro and in vivo in terms of selectivity, potency and pharmacokinetics and show very favourable properties. Moreover, Trypanosoma brucei's phosphofructokinase enzyme - compounds interaction have been very well studied by numerous crystal structures which would allow them to be easily modified to further improve properties. BENEFITS  Novel validated target, well characterised mechanism of action and excellent structure-activity relationship  Compounds effective against both subspecies of the parasite and both stages of the disease  Orally bioavailable and able to cross the blood brain barrier in favourable proportions  Safe and effective in a mouse model with very short treatment duration (1-2 days)  Very fast time to completely kill the parasite (minutes vs days for other drug classes)  Can be used in combination with current medicines as they have a different mechanism of action
Submission ID: 3141,  Publication date: 2018-05-15
Development and Validation of a Novel Leishmania donovani Screening Cascade for High-Throughput Scrteening Using a Novel Axenic... 
A novel axenic amastigote Leishmania assay was developed and validated that reports only cytocidal molecules. It was used to screen a diversity-oriented synthesis library and two new chemical series with antileishmanial activity were identified. The new axenic assay has a significantly improved translation to the intracellular assay.
Submission ID: 3101,  Publication date: 2016-09-28
Antiprotozoal activity profiling of approved drugs: a starting point toward drug repositioning. DNDi data is made available her... 
A set of 100 registered drugs with drug repositioning potential for neglected diseases was assembled and tested in vitro against four protozoan parasites.
Submission ID: 3021,  Publication date: 2015-09-08
Moxidectin 
Moxidectin (cydectin) is a milbemycin class drug used as an antiparasiticide in animals.
Submission ID: 1501,  Publication date: 2015-08-12
Selamectin 
Selamectin is the active in the product, Revolution.
Submission ID: 1502,  Publication date: 2015-08-12
Doramectin 
Doramectin (Dectomax) is a commercial antiparasitic for livestock.
Submission ID: 1521,  Publication date: 2015-08-12
Espirantel 
Cestex (espirantel) is an oral medication for animals (dog/cat)for the treatment of helminthes.
Submission ID: 1541,  Publication date: 2015-08-12
Methods for Synthesizing Vinly Sulfones 
Efficient and affordable regioselective methods for the synthesis of vinyl sulfones. In particular, methods for synthesizing (E)-vinyl sulfones for use in the synthesis of the protease inhibitor K777 and various analogs thereof. K777 has been shown to be safe and efficacious in animal models of acute and chronic Chagas disease.
Submission ID: 3001,  Publication date: 2014-10-01
protein microarray for identifying biomarkers for potential use in malarial parasite diagnostics and vaccine development. 
At the National Institute of Parasitic Diseases Dr. Jun-Hu Chen and others have developed a protein microarray that can be used for identifying biomarkers for potential use in malarial parasite diagnostics and vaccine development.
Submission ID: 2961,  Publication date: 2014-08-25