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BioAssay: AID 485343

Summary of small molecule inhibitors of UBC13 Polyubiquitin

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are a family of adapter proteins that bind an unusual ubiquitin-conjugating enzyme, Ubc13, which produces polyubiquitin chains linked at lysine 63 of ubiquitin. These lysine 63-linked ubiquitin polymers trigger changes in protein activity. Ubiquitination by Ubc13 of TRAFs and the various protein kinases to which TRAFs bind is recognized as more ..
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AID: 485343
Data Source: Burnham Center for Chemical Genomics (SBCCG-A443-UBC13-Summary-Assay)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
BioAssay Version:
Deposit Date: 2010-10-04
Modify Date: 2011-04-25
Target
Related Experiments
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AIDNameTypeComment
485273uHTS identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET AssayScreeningdepositor-specified cross reference: Primary Screen
488856Single concentration confirmation of UBC13 Polyubiquitin Inhibitors using a Caspase-3 counter screenScreeningdepositor-specified cross reference
488859Single concentration confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET AssayScreeningdepositor-specified cross reference
493155Dose Response confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET AssayConfirmatorydepositor-specified cross reference
493182Dose Response confirmation of uHTS for the identification of UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay reconfirmConfirmatorydepositor-specified cross reference
504680SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreenConfirmatorydepositor-specified cross reference
504685SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreenConfirmatorydepositor-specified cross reference
504687SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET AssayConfirmatorydepositor-specified cross reference
504689Dose Response confirmation of UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreenConfirmatorydepositor-specified cross reference
588375SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 2Confirmatorydepositor-specified cross reference
588376SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 2Confirmatorydepositor-specified cross reference
588390SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 2Confirmatorydepositor-specified cross reference
602205SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 3Confirmatorydepositor-specified cross reference
602206SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 3Confirmatorydepositor-specified cross reference
602207SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 3Confirmatorydepositor-specified cross reference
602400SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Bfl-1 counterscreen - Set 4Confirmatorydepositor-specified cross reference
602401SAR Analysis of small molecule UBC13 Polyubiquitin Inhibitors using a Caspase-3 counterscreen - Set 4Confirmatorydepositor-specified cross reference
602404SAR analysis of small molecule UBC13 Polyubiquitin Inhibitors via a TR-FRET Assay - Set 4Confirmatorydepositor-specified cross reference
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Number: 1R03 MH085677-01
Assay Provider: Dr. John C. Reed, Sanford-Burnham Medical Research Institute, San Diego CA

Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are a family of adapter proteins that bind an unusual ubiquitin-conjugating enzyme, Ubc13, which produces polyubiquitin chains linked at lysine 63 of ubiquitin. These lysine 63-linked ubiquitin polymers trigger changes in protein activity. Ubiquitination by Ubc13 of TRAFs and the various protein kinases to which TRAFs bind is recognized as a critical step in signaling by TNFRs, TLRs, NLRs, and T-cell and B-cell antigen receptors (TCR/BCR) during innate and acquired immune responses. Since aberrant signaling by these receptor systems is linked to a wide variety of autoimmune, inflammatory, and infectious diseases; compounds that neutralize Ubc13 may prove useful as a novel type of immunosuppressive or anti-inflammatory agent.

REFERENCES
1. Fukushima, T., Matsuzawa, S., Kress, C. L., Bruey, J. M., Krajewska, M., Lefebvre, S., Zapata, J. M., Ronai, Z., and Reed, J.C. (2007) Proc Natl Acad Sci USA 104(15), 6371-6376 (PMC1851032)
2. Yamamoto, M., Okamoto, T., Takeda, K., Sato, S., Sanjo, H., Uematsu, S., Saitoh, T., Yamamoto, N., Sakurai, H., Ishii, K. J., Yamaoka, S., Kawai, T., Matsuura, Y., Takeuchi, O., and Akira, S. (2006) Nat Immunol 7, 962-970
3. Yamamoto, M., Sato, S., Saitoh, T., Sakurai, H., Uematsu, S., Kawai, T., Ishii, K. J., Takeuchi, O., and Akira, S. (2006) J Immunol 177, 7520-7524
4. Akira, S., Takeda, K., and Kaisho, T. (2001) Nat Immunol 2, 675-680
5. Chen, Z. J. (2005) Nat Cell Biol 7, 758-765
6. Karin, M., and Ben-Neriah, Y. (2000) Ann Rev Immunol 18, 621-663
7. Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., and Chen, Z. J. (2000) Cell 103, 351-361
8. Wooff, J., Pastushok, L., Hanna, M., Fu, Y., and Xiao, W. (2004) FEBS Lett 566, 229-233
9. Wu, H., and Arron, J. R. (2003) Bioessays 25, 1096-1105
10. McKenna, S., Hu, J., Moraes, T., Xiao, W., Ellison, M. J., and Spyracopoulos, L. (2003) Biochemistry 42, 7922-7930
11. Hau, D. D., Lewis, M. J., Saltibus, L. F., Pastushok, L., Xiao, W., and Spyracopoulos, L. (2006) Biochemistry 45, 9866-9877
Protocol
Please see pertinent AIDs: 485273, 504680, 504685, 504687
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100. Testing has not progressed to the point where a probe molecule has been identified.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML307
PubChem Substance ID (SID) for probe 1: 134958980
PubChem Compound ID (CID) for probe 1: 56639556
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 781 +/- 10
Target for probe 1: UBC13 (gi: 4507793)
Disease relevance for probe 1: Inflamation, Immune Response
Anti-target for probe 1: Caspase 3; SHProtease Counterscreen
Fold selectivity for probe 1: >128
NCBI Book chapter link for probe 1: http://www.ncbi.nlm.nih.gov/books/NBK143542/ (ID: 3035976)
Grant number for probe 1: MH085677-01
NCBI Book chapter title for probe 1: Selective UBC 13 Inhibitors
Additional Information
Grant Number: 1R03 MH085677-01

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