Core D is critical for the central tenet ofthe UCLA-CMCR, which is that classes of mitigators of radiation damage can be identified by their chemical structures and/or the biological pathways that they utilize. Core D has provided and will continue to provide the technological driving force behind the work ofthe projects in high-throughput screening (HTS) of small molecule libraries with the aim of discovering novel mitigators of radiation damage. Core D centralizes HTS in a state-of-the-art facility that has already proven its value to the UCLA-CMCR, with several families of lead compounds identified. Additionally, in order to deal with the data that has been generated and to provide it to the CMCR in a form in which it can be mined for structureactivity relationships and other relevant chemical and biological information Core D, through pilot research funding, has established a relationship with Collaborative Drug Discovery (CDD) to use its an industrialstrength database for these purposes. Access to this data is available to other CMCRs. Now that families of lead compounds have been identified, with more to come. Core D has been further expanded to include pharmaceutical chemists under Dr. Jung, who will play a central role in design and synthesis of analogues of active compounds to identify chemical structures responsible for activity, to improve their drug-like qualities, and their efficacy. This relationship also was initiated through pilot research funding. Finally, Core D provides proteomics primarily in the form of mass spectrometry to seek molecular signatures ofthe biological pathways utilized by effective mitigators so as to probe mechanism of action of these compounds.
Core D brings technology that allows us to measure the effects of many thousands of compounds on the response of cells to radiation so as to discover novel agents;an industrial-strength database to house the data and explore it to derive information;the ability to chemically improve active compounds and investigate structure-activity relationships;and to define the pathways by which they bring about their effects.
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|Purbey, Prabhat K; Scumpia, Philip O; Kim, Peter J et al. (2017) Defined Sensing Mechanisms and Signaling Pathways Contribute to the Global Inflammatory Gene Expression Output Elicited by Ionizing Radiation. Immunity 47:421-434.e3|
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