SCREENING AND CHEMICAL INFORMATICS CORE: Screening Informatics: The key deliverables of the MLPCN are public data of high quality, published to PubChem, and supported chemical probe development. This mission requires two essential components, an Operational Environment for data management and quality assurance, and a Knowledge Environment facilitating efficient chemical probe optimization. The TSRI Center has these comprehensively on a production scale and will make key tools available broadly to maximize the impact of the MLPCN effort. We will also act quickly to implement policies and procedures recommended by the MLPCN steering committee. During MLSCN pilot phase, the informatics environment (described in Facilities and Other Resources), which is a critical and unifying link between La Jolla and Florida, has successfully managed assays on our institutional library, which exceeds 600,000 individual compounds, as well as >35 assays against the MLSMR 60-200K screening set. A metric of our current capabilities was the deposition of 80 assays with distinct AID's into PubChem. Automated submission to PubChem occurred within 5 +/- 4 days (mean/SD) of the completion of scientific Quality Assurance within the TSRI Center. The MLPCN mission will be supported by 3 Specific Aims for the Informatics Core:
Aim 1 : Maintain operational informatics infrastructure for MLPCN production phase.
Aim 2 : Knowledge Environment: Unlocking the efficiencies in probe development.
Aim 3 : Building the MLPC Network.
|Swingle, Mark; Volmar, Claude-Henry; Saldanha, S Adrian et al. (2017) An Ultra-High-Throughput Screen for Catalytic Inhibitors of Serine/Threonine Protein Phosphatases Types 1 and 5 (PP1C and PP5C). SLAS Discov 22:21-31|
|Dusaban, Stephanie S; Chun, Jerold; Rosen, Hugh et al. (2017) Sphingosine 1-phosphate receptor 3 and RhoA signaling mediate inflammatory gene expression in astrocytes. J Neuroinflammation 14:111|
|Darrah, Erika; Kim, AeRyon; Zhang, Xi et al. (2017) Proteolysis by Granzyme B Enhances Presentation of Autoantigenic Peptidylarginine Deiminase 4 Epitopes in Rheumatoid Arthritis. J Proteome Res 16:355-365|
|Buczynski, Matthew W; Herman, Melissa A; Hsu, Ku-Lung et al. (2016) Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure. Proc Natl Acad Sci U S A 113:1086-91|
|Ruiz de Sabando, Ainara; Wang, Chao; He, Yuanjun et al. (2016) ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer. Mol Cancer Ther 15:72-83|
|Nair, Reji N; Mishra, Jitendra K; Li, Fangzheng et al. (2016) Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors. Medchemcomm 7:900-905|
|Fanning, Sean W; Mayne, Christopher G; Dharmarajan, Venkatasubramanian et al. (2016) Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation. Elife 5:|
|Sanna, M Germana; Vincent, Kevin P; Repetto, Emanuela et al. (2016) Bitopic Sphingosine 1-Phosphate Receptor 3 (S1P3) Antagonist Rescue from Complete Heart Block: Pharmacological and Genetic Evidence for Direct S1P3 Regulation of Mouse Cardiac Conduction. Mol Pharmacol 89:176-86|
|Wood, Michael R; Noetzel, Meredith J; Tarr, James C et al. (2016) Discovery and SAR of a novel series of potent, CNS penetrant M4 PAMs based on a non-enolizable ketone core: Challenges in disposition. Bioorg Med Chem Lett 26:4282-6|
|Teijaro, John R; Studer, Sean; Leaf, Nora et al. (2016) S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-? autoamplification. Proc Natl Acad Sci U S A 113:1351-6|
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