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High Throughput Screening (HTS) • Compound library collection of ~300,000• Liquid Handling: Labcyte Echo 555, Biomek FX workstation, TTP Labtech’s Mosquito HTS XI• Cell Biology: Thermo Fisher Cytomat, Nuaire C02 water jacketed incubators, Guava EasyCyte Plus Flow Cytometer• Assay Detection: MDS SpectraMax Plus UV/Visible light absorbance plate reader, MDS SpectraMax Gemini XS florescence plate reader• Nexus Labstore, Covaris L8 compound dissolution instrument, Agilent PlateLoc Thermal Plate sealer
Medicinal Chemistry (MC) • Reverse phase high performance liquid chromatography using UV/visible absorption spectroscopy and mass spectrometry detection systems• Bruker Avance 400 MHz NMR instruments (x2), one equipped with Bruker B-ACS 60-sample automated sample changer• Facilitated access to Synthetic Chemical Biology Core Facility synthesis, analysis, purification, and compound management laboratories
Biotechnology Innovation & Optimization Center (BIOC)• Shimadzu 2010 LC systems with UV/Vis, fluorescence and diode array detectors• Applied Biosystems 3200 Q Trap LC/MS/ systems capable of small molecule analysis in complex matrices• Pilot plant with UniGlatt particle coating, tablet press, spray drier mixers, lyophilizer, isolated hoods, sterile formulation• Testing instruments for moisture, tonicity, viscosity, and many others
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Lead Development & optimization shared resource
A large portion of the Center’s research is conducted in partnership with the KU Cancer Center (KUCC) and the Institute for Advancing Medical Innovation (IAMI).
LDOSR Personnel
High Throughput Screening (HTS) – • Assay method development for biochemical, biophysical or phenotypic screens• Assay optimization for HTS adoption and assay validation• Large compound library HTS• Hit identification/confirmation/ prioritization
Medicinal Chemistry (MC) – • Synthesis and medicinal chemistry consultation• Application of structure-activity and structure-property relationship optimization• Identification of resources for compound synthesis for hit-to-probe, probe-to-lead and lead-to-preclinical candidate progression
Biotechnology Innovation & Optimization Center (BIOC) – • Drug delivery• Bioanalytical method development• In vitro pharmacology testing• In vivo pharmacokinetic and tissue distribution testing• Dosage-form development• Compound solubility and stability enhancement• Drug substance and dosage form analysis
Michael J. Baltezor, PhDDirectorLead Development & Optimization Shared ResourceDirectorBiotechnology Innovation & Optimization CenterMcCollum Research Laboratory785-864-1040mbaltezor@ku.edu
Anuradha Roy, PhDDirectorHigh Throughput Screening LaboratoryShankel Structural Biology Center785-864-1709anuroy@ku.edu
Frank Schoenen, PhDDirectorMedicinal Chemistry LaboratoryShankel Structural Biology Center785-864-1719schoenen@ku.edu
Melinda Broward, MSProject DirectorHigh Throughput Screening LaboratoryShankel Structural Biology Center785-864-1946mbroward@ku.edu
The Lead Development and Optimization Shared Resource (LDOSR) is a KU Cancer Center shared resource composed of high-throughput screening (HTS), medicinal chemistry (MC), and formulation drug delivery expertise (BIOC). The LDOSR provides support to investigators to accelerate projects from early development around cancer pathways or targets, through HTS hit prioritization, secondary in vitro assays (confirmatory, orthogonal, and counter screens), medical chemistry optimization, in vitro pharmacology testing, in vivo pharmacokinetics and drug delivery formulations for in vivo preclinical proof-of-concept testing. The services of the LDOSR are provided either as an integrated package through the Target Acceleration Steering Committee (TASC) or on a stand-alone basis to researchers based on specific project activities. Access to most critical core laboratories at both KU-Lawrence and KUMC campuses is facilitated through the TASC. Integrated service development plans assist researchers select the most appropriate testing needed to facilitate and accelerate development plans in grant applications and for optimized decision making.
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