Takeda will provide CIDR investigators with selected anti-apoptotic Bcl-2 family inhibitors for anti-parasitic drug discovery including P.falciparum, P.vivax, C.parvum, T.cruzi, Toxoplasma, and Leishmania sps. The investigators will test inhibitors in in vitro cell culture assays specific to each organism to identify candidates for further drug development. The next phase of this proposal will be to evaluate hit compounds in animal models.
MSD will provide a UCSF/UCSD researcher with HMG-CoA reductase inhibitors (statins) to screen against schistosomal worms. CIDR will attempt to solve the structure of the S. mansoni HMG-CoA reductase.
GSK provided Dr. Stuart with 61 isoleucyl tRNA synthetase inhibitors to screen against Trypanosoma brucei. This led to the identification of some promising compounds that were then re-screened by GSK researchers against T. cruzi and Leishmania donovani. The compounds did not show whole cell activity of further interest.
Alnylam Pharmaceuticals will provide a CIDR researcher with a set of siRNAs targeting a hepatocyte receptor. The siRNAs will be used to assess the result of knocking down the receptor on P. falciparum invasion of hepatocytes in vivo.
Dr. Kaushansky was interested in accessing a class of compounds targeting a specific host protein, as she had previously shown that activating this protein might be an effective therapeutic strategy against liver-stage malaria. BVGH connected Dr. Kaushansky with Pfizer, who provided a novel activator compound to support her antimalarial drug discovery efforts.