The focus of this group, directed by Camilo Rojas, is to develop assays which follow activities of biomolecules like enzymes, transporters and receptors in vitro. When ready, assays are used to screen for small molecules that would bring the desired effect (mostly inhibit) on the activity of the biomolecules. In close collaboration with the medicinal chemistry and the in vivo pharmacology colleagues at BSi NTP, screening “hits” are modified to improve on their drug-like properties while trying to keep their biological activity.
This involves a cyclical effort where hit analogs are synthesized by medicinal chemists and tested for biological activity by the assay development and in vivo pharmacology groups followed by the synthesis of new analogs. The assay group is also involved in evaluating compounds for their metabolic stability and their ability to reach biological matrices (e.g. plasma, brain) to elucidate their pharmacokinetic properties. This work is carried out in close collaboration with the in vivo pharmacology group.
The group is hopeful about the development of glutamate carboxypeptidase (GCPII) inhibitors for the treatment of neuropathic pain and of D-amino acid oxidase (DAAO) inhibitors to ameliorate symptoms of schizophrenia. The lead compounds are currently going through all the hurdles in order to make them amenable to clinical development.
Rojas feels fortunate to work with top scientists like Jesse Alt, an analytical biochemist, and Ajit Thomas and Marigo Stathis who are in charge of developing and implementing screens for various enzymes, transporters and receptors.
There are also two postdoctoral fellows: Rana Rais, a pharmacokinetics expert and Mariana Figuera-Losada, who is currently working on the development of assays to evaluate compounds for the treatment of NeuroAIDS.
Rojas says he highly prizes the ease with which the group collaborates with Hopkins’ legendarily collegial academics. Consider: Where Hopkins medical scientists might describe the intricacies of how pathologies develop in the human body and then propose agents that might affect the pathologies, the BSi NTP might develop assays that could test some of the more promising compounds - - effectively seeking avenues that can lead to practical drug discoveries for BSi partners in industry.
Rojas, Alt, Thomas and Stathis are among more than a dozen associates of Barbara Slusher in the NeuroTranslational Program. They are enthusiastic about the more robust collaborations borne from a closer association with full-time academics.