The Uppsala Drug Optimization and Pharmaceutical Profiling Facility (UDOPP)
The identification of drug candidates suitable for pre-clinical and clinical development involves not only obtaining sufficient potency, but also ensuring the compound’s ADME (absorption, distribution, metabolism, excretion) properties are consistent with obtaining efficacy in vivo. The Uppsala Drug Optimization and Pharmaceutical Profiling Facility (UDOPP) collaborates with drug discovery researchers to optimize compound series and deliver candidate drugs of the highest possible quality through the use of a battery of in vitro and in silico assays.
UDOPP is integrated into the Department of Pharmacy at Uppsala University and the work is carried out in the group of Drug Delivery lead by Prof. Per Artursson. The Drug Delivery group has over 20 years of experience in the area and has also developed several of the methods used for ADME studies. UDOPP is affiliated with the Chemical Biology Consortium Sweden (CBCS) and the SciLifeLab Drug Discovery and Development Platform (DDD-Platform).
The studies performed by UDOPP range from relatively straightforward measurements of parameters such as solubility, permeability and metabolic stability, to more advanced research projects dealing with biopharmaceutical classification, identification of transport mechanisms including P-glycoprotein and prediction of their influence on pharmacokinetics, mapping the drug-drug interactions with transport proteins and design of formulations for in vivo experiments.
The work performed is of a professional quality and is documented to the level required by our partners.
UDOPP can provide:
• Computational modeling and in silico models for estimation of ADME properties
• Determination and prediction of physico-chemical properties: LogP, LogD and pKa
• Determination of solubility (kinetic and thermodynamic) and its pH dependence
• ADME: Absorption, Distribution, Metabolism, Excretion
• Human plasma protein binding
• Chemical stability
• Cell Membrane Permeability (cell monolayer assays)
• Active cellular uptake and efflux (identification and characterization)
• Inhibition of active transport (transporter related drug-drug interactions, DDI)
• Metabolic stability
• Cytochrome P450 inhibition and induction (metabolism related DDI)
• Metabolic enzyme identification studies (reaction phenotyping)
• Evaluation of pharmacokinetic (PK) studies
• Physiological-based pharmacokinetics (PBPK)
• Biotransformation: metabolite profiling and identification
• Mass spectrometry (MS)
• Cell and molecular biology
• Isolation and characterization of primary human hepatocytes
• Integrated cell models for study human drug metabolism and transport processes
• Proteomics, measurement of abundance of drug metabolizing enzyme and drug transporters in human hepatocytes and in human tissues.
There are eight LAF- benches in the laboratory and one clean room. The laboratory is also equipped with two state of the art UPLC-MS/MS, flow cytometer, zeta sizer, liquid handling robotic systems, TopCount scintillation counter, confocal microscope etc.
There are several cell lines used in the laboratory including Caco-2, MDCK, 2/4/A1 and an array of HEK293 cell lines expressing a collection of the most important drug transporting proteins and/or metabolising enzymes. In addition human primary hepatocytes are also isolated in the laboratory on a weekly basis.
At UDOPP we have a number of computer models to predict a compound´s solubility, permeability and drug-drug interactions with several of the most important ABC (efflux) and SLC (uptake) transporters (based on data from our own in vitro assays). The predictivity of the models is usually around 80 %.
UDOPP considers all projects on a case-by-case basis. An all-inclusive budget is assigned for each project and is based on a full-time-equivalent (FTE) scientist model. When working with non-profit partners we aim to provide a cost and time structure that is suited to the individual projects needs and capacity.
Please visit our website for more information on our research and expertise: http://www.farmfak.uu.se/farm/udopp/index.html