Our laboratories offer a variety of assay platforms and instruments for cell-based assay services using western-blot, ELISAs approaches (electrochemiluminescence, chemiluminescence, fluorescence and colorimetry) and laser scanning confocal microscopy for the quantification of different cellular phosphorylated proteins (cellular kinase assays, etc..) and the identification of signaling pathways impacted by drugs for early drug discovery.
Mechanism of Action
We offer a variety of cell free and cell-based assays to assess the mechanism of action of small molecules including:
- Biolayer interferometry to measure biomolecular interactions between small molecules/proteins, peptides/proteins, protein/protein interactions for kinetic and binding affinity determination
- Cell free enzymatic assays (kinases, proteases, etc…)
- Overexpression and genetic suppression of the molecular target in cellular models for target validation and target engagement studies
- Identification of the protein targets for drugs following click chemistry
and a proteomic approach
PK/PD and Bioavailability
As part of PK studies, we can determine the bioavailability (following oral, intraperitoneal, subcutaneous, topical/epicutaneous delivery) of small molecules as well as their tissue distribution using a deuterated standard and an LC-MS/MS approach and identify compounds with oral bioavailability and BBB penetration potential.
The most convenient route of drug administration is peroral and requires drug molecules to be absorbed from the gastroinstestinal track and enter the systemic circulation. As a precursor to in vivo PK studies, we offer several in vitro cellular models to predict gastrointestinal absorption and blood-brain barrier (BBB) penetrability for small molecules as well as assays to identify potential interactions with drug transporters.
We are equipped for processing pathological specimens and performing various histological stains and immunostaining and produce image analysis/quantification of various histological markers in pathological specimen following light, fluorescence and laser scanning confocal microscopy for colocalization studies. Example of studies include the detection and quantification of amyloid plaques, degenerating neurites, microgliosis/astrogliosis, tau hyperphosphorylation/oligomerization/aggregation in animal models of Alzheimer’s disease; analysis of demyelination/immune cell infiltration in the spinal cord of a mouse model of MS, etc…
Medicinal Chemistry / SAR
We can provide various services for early drug discovery projects including:
- Click chemistry for target identification
- Synthesis of API and analogs
- Screening of compounds (focused library, diversity sets, etc…) using cell free and cell-based assays for the identification of hits/chemical scaffolds and the establishment of structure activity relationships (SAR) to orient the rational design of compounds with higher potency