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ADME (Absorption Distribution, Metabolism Excretion) of Therapeutics (UDOPP)

National facility

UDOPP2 - DMPKT picture

UDOPP is the DDD-platform facility for absorption, distribution, metabolism, excretion (ADME) and pharmaceutical profiling. UDOPP provides unique expertise and state-of the-art laboratory facilities to strengthen the hit collections and compound portfolio of Swedish academic groups. We add scientific value to all stages of the preclinical drug development process and we facilitate the selection of those drug candidate molecules with the greatest chance of reaching the market. UDOPP is a node within the world renowned Drug Delivery group at the Department of Pharmacy, Uppsala University and affiliated with the CBCS (Chemical Biology Consortium Sweden).

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 (metabolism related DDI).
  • Determination and prediction of physico-chemical properties. LogP, LogD 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

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

APPLICATIONS

  • Achiral Pyrazinone-Based Inhibitors of the Hepatitis C Virus NS3 Protease and Drug-Resistant Variants with Elongated Substituents Directed Toward the S2 Pocket.
  • In vitro and in vivo activities of 2-aminopyrazines and 2-aminopyridines in experimental models of human African trypanosomiasis.
  • Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice.
  • 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.

RECENT PROJECTS

Targeting MTH1 nucleotide triphosphatase prevents sanitation of oxidised dNTP pools and kills cancer cells.