Lead Development & Optimization Shared Resource

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LEAD DEVELOPMENT AND OPTIMIZATION SHARED RESOURCE (LDOSR): ABSTRACT The Lead Development and Optimization Shared Resource (LDOSR) is a shared resource of The University of Kansas Cancer Center (KUCC), composed of three component laboratories located on the KU Lawrence West Campus: High-Throughput Screening (HTS), Medicinal Chemistry (MDCM) and the Biopharmaceutical Innovation and Optimization Center (BIOC). LDOSR provides preferred access to KUCC members to accelerate projects from drug-target discovery through high-throughput screening, compound hit prioritization, secondary in vitro confirmatory assays, medical chemistry optimization, in vitro pharmacology testing, in vivo pharmacokinetics, and drug delivery formulations for in vivo preclinical proof-of-concept testing. The activities involved with the generation, evaluation, and optimization of drug candidates is an iterative process that crosses several scientific disciplines. The LDOSR has been structured to optimize services under a single, easy-to-access umbrella, with oversight from the Director and a team of project managers, allowing projects to move seamlessly between component laboratories. Comprehensive plans tailored to fit each project’s needs ensure users get the most relevant data to move their projects forward. Additionally, the LDOSR offers drop-in ready grant submission and publication language. Over the past five years (2016-2020), the LDOSR has supported 167 KUCC member projects (~76% were peer-review funded). The LDOSR leverages research infrastructure established, historically, through internationally recognized medicinal and pharmaceutical chemistry research conducted by the University of Kansas School of Pharmacy. Added to this is the availability of industry experienced scientists from former area Pharma and CRO companies. The LDOSR has successfully recruited top-notch scientists with industry and academic qualifications to lead and staff the three component laboratories. The LDOSR, working with the Associate Director for Translational Research, established the Drug Discovery and Development Steering Committee. This translational-research catalyst provides a forum for KUCC investigators to develop research concepts at the chemistry/biology interface with support from the LDO laboratories. The LDOSR partners with The Institute for Advancing Medical Innovation to advance drug discovery projects through early drug development, actively conducting and supporting studies necessary to enable first-in-human clinical trials. Additionally, LDOSR staff serve on the Investigator-Initiated Trial Steering Committee, which facilitates evaluation of development candidates in early phase experimental therapeutics trials conducted by the D3ET research program. Lastly, bioanalytical methods for determination of drug and metabolite concentrations in preclinical matrices, are transferred to the Clinical Pharmacology Shared Resource where they are cross-validated in human matrices under GLP conditions to support early phase clinical trials. The result is a fully integrated, end-to-end translational research function capable of advancing novel cancer therapeutic agents invented by KUCC members to clinical trials.