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Periodic Report Summary 1 - OCEANCHARCOT (Research of new marine inhibitors targeted against desease-relevant proteins kinases)

The outgoing phase of OCEANCHArCoT project held in Australia (Eskitis Institute for Drug Discovery, Brisbane, period 2014-2016). The aim was to identify new leads from marine chemodiversity to inhibit necroptosis pathway, which is related to neurodegenerative diseases, inflammatory diseases, allograft rejection etc. Three key proteins at the early stage of necroptosis (i.e initiators) were defined as priority at the beginning of the project (RIPK1, RIPK3 and MLKL). Due to the intrinsic characteristics of these targets, it was extremely difficult to produce a significant and stable amount of them. The original workflow had to be redefined to allow a rational and efficient exploration of marine chemodiversity from Great Barrier Reef biodiversity housed in Nature Bank (Eskitis Institute, Griffith University) despite the lack of target availability. With a cell-based assay that we developed for a robotic plateform to identify necroptosis inhibitors, we screened 35,585 Lead-Like Enhanced fractions corresponding to 7,117 marine biota. We obtained 102 hits form this screening. Then, strategy was to implement NMR fingerprint based dereplication to focus our workflow on the best potential leads. Dose-responses of 102 hits are currently in progress. Both results will allow choosing shortly around 10 active leads to continue the project. Over the pure scientific aspect of the project, the outgoing phase at The Eskitis Institute for Drug Discovery was the opportunity to gain strong skills on real high throughput screening, sample management and Lead-Like Enhanced fraction production. Moreover, in such scientific environment like Eskitis Institute, we learnt a lot about cutting edge technologies and strategies related to drug discovery. Indeed, a lot of projects run currently at The Eskitis Institute are highly competitive in the field of medicinal chemistry. Progressing in close proximity of leading scientists is also very positive to overcome our limits and build a strong qualified profile. Through the project, we had the opportunity to enlarge our network with scientists from world-class research institutes like The University of Queensland, Queensland Museum, Translational Research Institute Australia etc. OCEANCHArCoT project is definitely the beginning of a long-term collaboration between both research institutes. The ending goal is to reach clinical trials with few leads for a potential new drug on the market.


Any request regarding the project can be addressed to Dr Benoît SERIVE ( or to Dr Stéphane BACH ( Screening plateform KISSf CNRS/UPMC – USR3151, Station biologique de Roscoff, Place Georges Teissier, 29688 Roscoff Cedex, France.

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