Uppsala Drug Optimization and Pharmaceutical Profiling (UDOPP)

National facility

UDOPP1 - CBCS picture

UDOPP provides unique expertise and a state-of-the art laboratory for absorption, distribution, metabolism, excretion (ADME) investigations and pharmaceutical profiling of molecular probes and drug candidates. We add high scientific value to collaborative chemistry and biological discovery projects, and thereby increase the number of high-quality molecular probes and small molecules for life science applications. UDOPP is a node within the world renowned Drug Delivery group at the Department of Pharmacy, Uppsala University. We are affiliated with the Chemical Biology Consortium Sweden (CBCS) and the SciLifeLab Drug Discovery and Development Platform (DDD-Platform).

SERVICES

  • Active cellular uptake and efflux (identification and characterization).
  • ADME. Absorption, Distribution, Metabolism, Excretion
  • Bioanalysis.
  • Biopharmaceutics.
  • Biotransformation. Metabolite profiling and identification
  • Cell Membrane Permeability. Cell monolayer assay.
  • Chemical stability.
  • Computational modeling and in silico models for estimation of ADME properties.
  • Cytochrome P450 inhibition and induction studies.
  • Determination and prediction of physico-chemical properties. LogD, LogP and pKa
  • Determination of solubility (kinetic and thermodynamic) and its pH dependence.
  • Evaluation of pharmacokinetic (PK) studies.
  • Formulation.
  • Human plasma protein binding.
  • Inhibition of active transport (transporter related drug-drug interactions, DDI).
  • Integrated cell models for study human drug metabolism and transport processes.
  • Isolation and characterization of primary human hepatocytes.
  • Mass spectrometry (MS).
  • Metabolic enzyme identification studies (reaction phenotyping).
  • Metabolic stability.
  • Physiological-based pharmacokinetics (PBPK).
  • Proteomics. Measurement of abundance of drug metabolizing enzyme and drug transporters in human hepatocytes and in human tissues.

EQUIPMENT

  • Cellometer. (Vision CBA) combines non-fluidic image cytometry with flow analysis software for performing cell-based assays
  • Automated Liquid handling robotic station.
  • Cell Culture Laboratory.
  • Equipment for measurement of phys-chem properties (Sirius T3).
  • Ultra High Performance Liquid Chromatography triple quadrupole mass spectrometry (UHPLC/MS/MS, 2 instruments).

APPLICATIONS

  • Exploration and Pharmacokinetic Profiling of Phenylalanine Based Carbamates as Novel Substance P 1-7 Analogues.
  • Novel Peptidomimetic Hepatitis C Virus NS3/4A Protease Inhibitors Spanning the P2-P1.
  • Structure-Activity Relationships of Synthetic Cordycepin Analogues as Experimental Therapeutics for African Trypanosomiasis.
  • Constrained H-Phe-Phe-NH2 analogues with high affinity to the substance P 1-7 binding site and with improved metabolic stability and cell permeability.
  • The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox.
  • Profiling of drug metabolizing enzymes, drug transporters, their abundance and functionality in cancer tissues & cancer cell lines.