Endotherm is involved with the following research projects EUTrigTreat (an integrated EU-FP7-project): Cardiac arrhythmias are a major cause of death and morbidity. Current treatment and prevention strategies are empirically based, carry significant side effects and risks, and are costly. To address the challenging situation how diagnosis and treatment of an epidemically growing group of patients at increased risk for sudden cardiac death can be improved, new insights into genetic and environmental mechanisms of arrhythmia initiation as well as development of novel therapeutic strategies are urgently needed. Endotherm develops together with its consortium partners novel potential therapeutic drug candidates to be tested in cells and in vivo. The aim is to finally discover new effective drugs with fewer side effects and at moderate costs. The EUTrigTreat project is coordinated by the heart center of the Universität Göttingen (Prof. Dr. Stephan E. Lehnart). 12 academic institutions and besides Endotherm two additional small enterprises from overall nine countries are involved. EUGeneHeart (an integrated EU-FP6-project): Cardiovascular diseases are the most frequent cause of death in the EU. The EUGeneHeart project is coordinated by the department of Cardiology and Pneumology in the Heart Centre of the University Medicine Göttingen. Scientists from 23 institutions, located in 10 countries, are searching in common for reasons and possibilities for a better treatment and prevention of heart failure. The goal of the project is the development of new approaches to prevent and treat heart failure through analysis of the genomics of signalling. The strategy is based on the hypothesis that beneficial as well as maladaptive forms of hypertrophy exist and that heart failure is frequently preceded by maladaptive hypertrophy. Both adaptive and maladaptive signalling in hypertrophy are dissected to identify beneficial and maladaptive components of signal transduction in hypertrophy and heart failure with the aim to develop new treatments. Endotherm contributes to the project by providing its expertise and experience in medicinal chemistry and in drug discovery & development. Particularly, unique compound libraries and tailored modulators for newly discovered targets are synthesized and evaluated. Novel Inhibitors of MurA, an Antibacterial Target Enzyme The occurrence of infectious diseases has been increased dramatically during the past 20 years, due to antibiotic resistance, global warming and globalization (intense travelling). The aim of the joint research project, which is performed together with Prof. Dr. Ch. Klein at the Universität Heidelberg, is the development of new enzyme inhibitors which inhibit the formation of bacterial cell walls and thus act as antibiotics. Following the principle of rational drug design, Endotherm contributes by means of its outstanding experience in synthetic organic chemistry and modern drug discovery tools, and the group in Heidelberg applies its existing knowledge and experience with related enzymes and drug testing technologies. Poster Download Inhibitors of Dengue NS3 protease The Dengue virus (DENV) infects 50 million (WHO) to 100 million (NIH) people annually. Forty percent of the world's population, predominately in the tropics and sub-tropics, is at risk for infection by this virus. DENV infection can cause dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and finally death. The goal of the joint research project, which is performed together with Prof. Dr. Ch. Klein at the Universität Heidelberg, is to optimize an assay for the determination of activity of the Dengue virus protease NS3 under high-throughput conditions and to screen compound libraries for potential inhibitors which are intended to be used as lead compounds for further medicinal chemistry efforts. We already succeeded in optimizing the expression of Dengue NS3 in E. coli cells and are able to produce ambient amounts of the protease. The assay was optimized with respect to various factors (design of the substrate, buffer composition, fluorimetric detection) and was used for random and guided screening. The screening resulted in promising hits, one of them possesses all prerequisites for development towards a lead compound, such as high affinity, low molecular weight, and synthetic feasibility. This compound is, to our knowledge, the most potent non-peptidic inhibitor of Dengue NS3 reported to date. Poster Download