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BioAssay: AID 504878

Inhibitors of USP1/UAF1: Summary

Deubiquitinating enzymes (DUBs) are a class of enzymes that can cleave isopeptide bond formed between the C-terminal carboxylate of ubiquitin and a lysine side-chain amino group on the target protein. Among them, ubiquitin specific proteases (USPs) constitute the largest DUB family. Human USPs are emerging as promising targets for pharmacological intervention because of their connection to a more ..
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AID: 504878
Data Source: NCGC (USP1000)
BioAssay Type: Summary, Candidate Probes/Leads with Supporting Evidence
Depositor Category: NIH Molecular Libraries Probe Production Network
Deposit Date: 2011-06-29
Target
Related Experiments
Show more
AIDNameTypeComment
504865Inhibitors of USP1/UAF1: Pilot qHTSConfirmatorydepositor-specified cross reference
540327Inhibitors of USP1/UAF1: Hit Validation in Primary AssayConfirmatorydepositor-specified cross reference
624341Inhibitors of USP1/UAF1: Hit Validation in USP7 Diubiquiting Gel AssayOtherdepositor-specified cross reference
624345Inhibitors of USP1/UAF1: Hit Validation in USP2 Diubiquiting Gel AssayOtherdepositor-specified cross reference
624346Inhibitors of USP1/UAF1: Hit Validation in USP1 Diubiquiting Gel AssayOtherdepositor-specified cross reference
651605Inhibitors of USP1/UAF1: SAR in Primary AssayConfirmatorydepositor-specified cross reference
651621Inhibitors of USP1/UAF1: SAR in USP1/UAF1 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
651622Inhibitors of USP1/UAF1: SAR in USP46/UAF1 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
651623Inhibitors of USP1/UAF1: SAR in USP8 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
651624Inhibitors of USP1/UAF1: SAR in USP7 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
651625Inhibitors of USP1/UAF1: SAR in USP5 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
651626Inhibitors of USP1/UAF1: SAR in USP2 diubiquitin SDS-PAGE gel assayOtherdepositor-specified cross reference
743255Inhibitors of USP1/UAF1: Primary ScreenConfirmatorydepositor-specified cross reference
Description:
Deubiquitinating enzymes (DUBs) are a class of enzymes that can cleave isopeptide bond formed between the C-terminal carboxylate of ubiquitin and a lysine side-chain amino group on the target protein. Among them, ubiquitin specific proteases (USPs) constitute the largest DUB family. Human USPs are emerging as promising targets for pharmacological intervention because of their connection to a number of human diseases, including prostate, colon and breast cancer (1, 2), pediatric acute lymphoblastic leukemia (3), and familial cylindromatosis (4). The advantage of inhibiting USPs lies in the potential specificity of therapeutic intervention that can lead to better efficacy and reduce nonspecific side effects.

In a collaboration between the University of Delaware and the NIH Chemical Genomics Center, a high-throughput screen assay was developed to screen for USP1/UAF1 inhibitors. This miniaturized assay has a fluorescent read-out and is used to screen the NIH Molecular Libraries Small Molecule Repository (MLSMR) in order to identify a small molecule that inhibits USP1. Follow-up assays have also been developed to further test the hits from the primary screen.

NIH Chemical Genomics Center [NCGC]
NIH Molecular Libraries Probe Centers Network [MLPCN]

MLPCN Grant: DA030552-01
Assay Submitter (PI): Zhihao Zhuang, University of Delaware

1. Priolo, C., et al. (2006) The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Res 66, 8625-8632

2. Popov, N., et al. (2007) The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol 9, 765-774

3. De Pitta, C., et al. (2005) A leukemia-enriched cDNA microarray platform identifies new transcripts with relevance to the biology of pediatric acute lymphoblastic leukemia. Haematologica 90, 890-898

4. Kovalenko, A., et al. (2003) The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature 424, 801-805
Protocol
Please see linked AIDs for a detailed protocol for a specific assay.
Comment
This project is on-going and will be updated at a later point with findings.
Categorized Comment - additional comments and annotations
From MLP Probe Report:
Probe count: 1
MLP Probe ML# for probe 1: ML323
PubChem Substance ID (SID) for probe 1: 144116952
PubChem Compound ID (CID) for probe 1: 60167849
Probe type for probe 1: Inhibitor
IC50/EC50 (nM) for probe 1: 76
Target for probe 1: USP1/UAF1 (gi: 118600387)
Disease relevance for probe 1: Cancer
Anti-target for probe 1: USP2; USP5; USP7; USP8; USP46/UAF1
Fold selectivity for probe 1: 1500
Grant number for probe 1: DA030552
Additional Information
Grant Number: DA030552

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