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 ..
Target
| Sequence: USP1 protein [Homo sapiens] Protein Family: Peptidase_C19 Gene:USP1 Related Protein 3D Structures |
Depositor Specified Assays
Show more |
| AID | Name | Type | Comment |
|---|---|---|---|
| 504865 | Inhibitors of USP1/UAF1: Pilot qHTS | confirmatory | |
| 624345 | Inhibitors of USP1/UAF1: Hit Validation in USP2 Diubiquiting Gel Assay | other | |
| 540327 | Inhibitors of USP1/UAF1: Hit Validation in Primary Assay | confirmatory | |
| 624346 | Inhibitors of USP1/UAF1: Hit Validation in USP1 Diubiquiting Gel Assay | other | |
| 624341 | Inhibitors of USP1/UAF1: Hit Validation in USP7 Diubiquiting Gel Assay | other | |
| 651605 | On Hold | ||
| 651621 | On Hold | ||
| 651622 | On Hold | ||
| 651623 | On Hold | ||
| 651624 | On Hold | ||
| 651625 | On Hold | ||
| 651626 | On Hold |
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
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.
Additional Information
Grant Number: DA030552
PageFrom: