Dear colleagues,

       I am a CNRS researcher leading a team working on protein kinases, 
with special focus on the search for, identification, optimization and 
characterization of pharmacological inhibitors of disease-relevant 
kinases such as cyclin-dependent kinases (CDKs), glycogen synthase 
kinase-3 (GSK-3), casein kinase 1 (CK1), etc. Most of our inhibitors 
have been co-crystallized with their kinase targets. Our first drug, 
roscovitine, is currently in late phase 2 clinical trials against non 
small cell lung cancer and nasopharyngal cancer. We hope to have a 
second drug in clinical trial next year against some renal diseases with 
no current treatment. Most of our papers are available as pdf files on 
our website.

       During the last few years we have worked on an orthologue of 
GSK-3 in /Plasmodium falciparum/. We have published only one paper so 
far in this field. Yet we have intensively (4 years !) screened for 
selective inhibitors of PfGSK-3 and have discovered a class of molecules 
that exquisitely inhibit PfGSK-3 and are totally inefficient on 
mammalian GSK-3. I feel that this unique selectivity is quite promising, 
although we clearly need to do more chemistry to improve the compounds 
down to nanomolar IC50 values (we are now around 0.2-0.4 uM).

       Given the conservation of GSK-3 sequence among the different 
//Plasmodium //species, I suspect that they will all be sensitive to our 
inhibitors, which would be quite interesting in terms of potential 
therapeutic applications. We are currently expressing GSK-3 from 4 other 
species of /Plasmodium /(/vivax, knowlesi, berghei/). Very interestingly 
we found that GSK-3 from /Leishmania /(/donovani /and /major/) and 
/Trypanosoma /(/brucei /and /cruzi/) are not sensitive to our 
inhibitors. We are currently collecting GSK-3 clones from as many 
species as possible (covering appropriate & diverse branches of the tree 
of life) to identify where GSK-3 becomes sensitive to our class of 
compounds.

       I am just wondering if anyone would have and be so kind as to 
send me a clone of the  GSK-3 orthologue in /Dictyostelium discoideum/ 
to express the kianse and evaluate its sensitivity to our inhibitors. Of 
course, if by chance, you happen to have clones of GSK-3 from other 
organisms (in particular unicellular parasites), I would be most 
interested to make use of them !

         Many thanks for your appreciated help and best wishes for your 
work,

         Laurent Meijer

-- 
Laurent Meijer
Protein Phosphorylation & Disease
CNRS
Station Biologique
Place Georges Teissier
B.P. 74
29682 ROSCOFF
FRANCE

tel: 33 (0)2 98 29 23 39
fax: 33 (0)2 98 29 25 26
email: [log in to unmask]

Web-site: www.sb-roscoff.fr/CyCell/