This is the first resource to provide researchers in academia and industry with an urgently needed update summarizing the current knowledge and possibilities for drug intervention against Trypanosomatides all in one volume. As such, it covers every aspect of the topic from basic research findings, via current treatments to translational approaches in drug development and includes both human and livestock diseases. The outstanding editor and contributor team reads like a Who?s Who of the field, thus guaranteeing the outstanding quality of this ready reference.
TOC:
Part One: Disease Burden, Current Treatments and Medical Needs (including disease models) and strategic approaches:
- History and critical assessment of Drug Discovery towards Kinetoplastida (Duszenko)
-
African Sleeping sickness (Croft)
-
Chagas? Disease (McKerrow)
-
Visceral, mucocutaneous and cutaneous Leishmaniasis (Ilg)
-
Veterinarian diseases (Alunda)
(Each disease to be covered according to the above key words)
-
CDD database (Sean Ekins)
- PPP and Drug Development (DNDi, Rob Don)
- Academic Drug Discovery efforts towards Kinetoplastida (Paul Wyatt, Dundee)
Part Two: Metabolic Peculiarities in the Trypanosomatid Family Guiding Drug
discovery:
- Proteolytic systems (Mottram)
- Gycosomal enzymes (Opperdoes;
- The trypanothione system (Fairlamb)
- Other unusual redox events (Krauth-Siegel)
- The selenoproteom (Gladyshev)
- The kinetoplast kinom (Zilberstein)
- The replicative machinery (Shlomai)
- Isoprenoid Biosynthesis (Urbina)
- RNA metabolism (Clayton)
- Apoptosis- and autophagy-related events (Duszenko)
- Leishmania-host interaction (Moll)
- Kinetoplastida metabolomics (Mike Barrett, Glasgow)
- Kinetoplastida novel transporters and resistance (Harry de Koning, Glasgow)
Part Three: Validation and Prioritization of Drug Targets in Kinetoplasts
- Cruzipain and related proteases (Mottram;
Coombs)
- Peroxiredoxins and related peroxidases (Castro, Tomas;
Wilkinson)
- Protein Kinases (Boshardt)
- Disulfide Reductases (trypanothione reductase, tryparedoxins) (Krauth-Siegel;
Comini)
- Trypanothione synthetase (Comini;
Fyfe;
Fairlamb)
- The glyoxalase system (Cordeiro)
- Enzymes of steroid synthesis (Urbina)
- Myristoyl transferase (Brenk)
- Enzymes of folate metabolism (Fairlamb)
- Glycosomal enzymes (Opperdoes;
- Glucos-6-phosphate dehydrogenase (Comini;
Ortiz)
- Tryp Transporters (Francisco Gamarro, Granada)
Part Four: Examples of structure-based rational design
- Trypanothione reductase inhibitor design (Beig, Selzer, Krauth-Siegel;
Botta)
- Trypanothione synthetase inhibitor design (Koch;
Jäger;
Fairlamb; others)
- Myristoyl transferase inhibitor design (Brenk;
Fairlamb)
- Protease inhibitor design (UCSF, McKerrow, Steverding or Augustyns;
Maes)
Part Five: Compounds under consideration or development
- 1,4-Naphthoquinones (Davioud Charvet)
- 4-Aminoquinolines (Loiseau)
- Antifolates (Costi;
Fairlamb)
- Phosphinic dipeptide inhibitors
- Paullones (Kunick)
- Others (Gamarro;
Robert Jacobs, Scynexis Inc. and Nigel Yarlett, Pace Univ.)
- In vitro and in vivo testing (Reto Brun Basel)