iNovacia, an internationally established contract research company owned by Kancera AB (Nasdaq OMX Stockholm First North, KAN), announces today the first results from the open collaboration in which the carefully designed iNovacia fragment collection consisting of ca 1,000 highly soluble, diverse and low molecular weight chemical scaffolds has been used to cross-validate the two biophysical techniques as fragment screening techniques. PARP15, a putative drug target, was used as target protein.
The iNovacia fragment collection has been screened for binding against PARP15 by surface plasmon resonance (BiacoreTM T200) at GE Healthcare and 14 out 15 fragment binders were possible to confirm by nuclear magnetic resonance (NMR) methods at iNovacia. The PARP15 protein was produced at MBB. The structures of the confirmed hits will be published.
Thomas Olin, CEO of iNovacia and Kancera, comments: “The collaboration with GE Healthcare and MBB has been highly productive, so far resulting in a technical cross-validation valuable both for GE Healthcare and iNovacia. In addition, the high quality of iNovacia´s fragment collection has yet again been confirmed”.
About fragment screening
Fragment screening as a complement or an alternative to conventional high-throughput screening (HTS) is currently attracting much attention from the pharmaceutical and biotech industry. In this approach, compounds that are smaller, have less functionality and are correspondingly weaker binders than most hits from HTS are screened by biophysical techniques. The number of compounds screened is much smaller (typically <1,000) since low complexity compounds have a higher probability of matching a target protein binding site. Further, a high proportion of the atoms in a fragment hit are directly involved in the desired protein-binding interaction, i.e. they are efficient binders. Starting the chemical optimisation stage with a highly soluble, low-molecular mass fragment is likely to produce lead compounds with advantageous physicochemical properties.
The human Poly-(ADP-ribose)-polymerases (PARPs) comprise a family of 17 proteins that all share a catalytic PARP domain. PARP activity is involved in processes such as transcription control and DNA repair. Inhibition of PARP activity is a promising strategy for cancer therapy and several PARP1 inhibitors are in clinical trials for the treatment of cancer. The other members of the PARP family are less studied but are clearly potential future drug targets.
iNovacia provides high-throughput screening, fragment-based screening and other drug discovery services to translate targets into validated leads for pharmaceutical and biotech companies. Enabled by a 300,000 compound library of highest international standard, unique biophysical tools for characterization of mode-of-action and SAR, iNovacia minimizes the technical risk and optimize lead-time and quality of drug discovery projects. iNovacia is a wholly owned subsidiary of Kancera AB (Nasdaq OMX Stockholm First North, KAN).