Abstract

D6.0 SELECTIVITY PROFILING CORE: A key challenge to the MLPCN strategy is the need to have sufficient capacity for selectivity screening data, essential for the optimization of selective chemical probes. The TSRI Center has instituted two generic approaches that enable these data to be developed and integrated in chemical optimization for broad ranges of biological targets. This area is one example of Center-driven scientific choices that have been of high value and impact broadly. Two such approaches, one for transcription and one for broad profiling of enzyme inhibition by catalytic family, are reduced to practice and presented.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54MH084512-02
Application #
7945399
Study Section
Special Emphasis Panel (ZRG1)
Project Start
Project End
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
2
Fiscal Year
2009
Total Cost
$610,844
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

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
Wood, Michael R; Noetzel, Meredith J; Engers, Julie L et al. (2016) Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core. Bioorg Med Chem Lett 26:3029-3033
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

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