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.