Discovery Teams

  • Objective:

    Development of small molecule in vitro probes, in vivo tool compounds and IND-ready preclinical candidates through high-throughput, iterative medicinal chemistry 

    Technology:

    • Matrix/Parallel library synthesis 

    • Modern Synthetic Technologies: Microwave (Biotage), Photo-redox and Electrochemical synthesis 

    • High-throughput Purification Technologies: (Waters LCMS, - Gilson HPLC, Biotage, Teledyne Isco) 

    • Supercritical Fluid

    • Chromatography (SFC) for chiral HPLC (analytical and preparative) 

      Innovation

    • Specially curated chemical building block collection for neuroscience targets.

    • Real-time incorporation of in vitro and in vivo DMPK data into SAR.  

    • Development of intellectual property (IP) in parallel with tools for academic discovery.

  • Objective:

    Provide primary screening, assay development, high-throughput screening (HTS) and detailed in vitro pharmacological analysis of small molecule ligands.  

    Technology/Techniques:

    • Hamamatsu FDSS (µCell) screening platform 
      Agilent BRAVO liquid handler 

    • Beckman Coulter ECHO 650 acoustic liquid handler 

    • EnVision 2105 Multimode Microplate Reader 

    • Ca2+ mobilization fluorescence assay 

    • GIRK/Thallium Flux assay 

    • Radioligand displacement assays 

      Innovation

    • Dotmatics Knowledge Solutions for cloud-based analysis and storage of assay data. 

    • Triplicate Screening technology to capture 3 modes of ligand pharmacology in one 4 min assay. 

    • Weekly data generation and reporting to inform SAR for the next round of screening. 

  • Objective:

    Provide in vitro and in vivo absorption, distribution, metabolism, and excretion (ADME) characterization of small molecule ligands including projected human dosing and drug-drug interaction liabilities.  

    Technology/Techniques

    • Sciex Triple quadrupoles (4500 with Agilent autoinjector & two 4000’s with LEAP autoinjector PAL HTC)  

    • Sciex QTRAP (5500) with LEAP autoinjector PAL HTC 

    • Tecan Freedom EVO and Agilent Bravo robotic liquid handler 

    • In vitro Clearance; plasma and brain homogenate binding assay  

    • Cytochrome P450 inhibition 

    • Bioanalysis of in vivo PK samples (brain and plasma) 

    • Identification of Metabolites (human/rat)  

      Innovation

    • DMPK group typically not found in academic institutions that mimics industrial small Biotech. 

    • Full in vitro and in vivo ADME profiling to de-risk preclinical candidates and make early “Go/ No-Go” decisions. 

    • Understand mechanisms of clearance and pharmacokinetic/pharmacodynamic (PK/PD) relationships for maximal efficacy on target. 

  • Objective:

    Provide pharmacological characterization of small molecule ligands in established preclinical models of central nervous system (CNS) disorders including schizophrenia (Sz), Parkinson’s Disease (PD), dystonia, and Alzheimer’s Disease (AD) 


    Technology/Techniques:

    • Assay evaluating antipsychotic-like activity: Amphetamine- or MK-801 Induced hyperlocomotion, PPI, CAR 

    • Assays to assess cognitive function:  NOR, conditioned fear, RAM, MWM  

    • Assays to evaluate efficacy in movement disorders: HIC, 6-OHDA lesion forelimb asymmetry, rotarod, automated gait analysis 

    • Assays to evaluate pain: von Frey, Hargreaves, formalin test 

    • Assays to assess addiction:  Self administration, CPP 

    • Genetic/humanized rodent models of Alzheimer’s disease 

    • Dosing/collection of in life PK samples for DMPK 


      Innovation:

    • Develop strong pharmacokinetic/pharmacodynamic relationships in various animal models for GPCRs and related targets. 

    • Support biomarker strategies (i.e. EEG, phMRI, PET) in preclinical models. 

    • Evaluate early stage, preclinical toxicology and safety pharmacology for pre-IND candidates.