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ubiquitin specific peptidase 1

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Target not currently curated in GtoImmuPdb

Target id: 2428

Nomenclature: ubiquitin specific peptidase 1

Family: C19: Ubiquitin-specific protease

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 785 1p31.3 USP1 ubiquitin specific peptidase 1
Mouse - 784 4 C6 Usp1 ubiquitin specific peptidase 1
Rat - 784 5q33 Usp1 ubiquitin specific peptidase 1
Previous and Unofficial Names Click here for help
deubiquitinating enzyme 1 | ubiquitin carboxyl-terminal hydrolase 1 | ubiquitin specific protease 1 | ubiquitin thioesterase 1 | ubiquitin thiolesterase 1
Database Links Click here for help
Specialist databases
MEROPS C19.019 (Hs)
Other databases
Alphafold
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 3.4.19.12

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
KSQ-4279 Small molecule or natural product Hs Inhibition 7.0 – 8.0 pIC50 1
pIC50 7.0 – 8.0 (IC50 1x10-7 – 1x10-8 M) [1]
Description: Binned IC50 from patent
ML323 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.1 pIC50 2
pIC50 7.1 (IC50 7.6x10-8 M) [2]
SJB2-043 Small molecule or natural product Hs Inhibition 6.3 pIC50 4
pIC50 6.3 (IC50 5.44x10-7 M) [4]
compound 61 [PMID: 36221183] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.9 pIC50 5
pIC50 5.9 (IC50 1.37x10-6 M) [5]
General Comments
USP1 has been shown to promote the survival of cancer cells by facilitating DNA repair. USP1 is an active oncology drug target. USP1 inhibition is proposed as an alternative to PARP inhibition, in particular for cancers that develop resistance to PARP inhibitors or are resistant to it. The experimental inhibitor ML323 has been used to confirm potential utility of USP1 inhibition in cancer models [2-3,6-7]. KSQ Therapeutics' KSQ-4279 is in early stage clinical development.

References

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1. Brenneman JB, Krall EB, Schlabach M, Wylie AA. (2020) Substituted pyrazolopyrimidines and substituted purines and their use as ubiquitin-specific-processing protease 1 (usp1) inhibitors. Patent number: WO2020132269A1. Assignee: KSQ Therapeutics, Inc.. Priority date: 20/12/2018. Publication date: 25/06/2020.

2. Dexheimer TS, Rosenthal AS, Luci DK, Liang Q, Villamil MA, Chen J, Sun H, Kerns EH, Simeonov A, Jadhav A et al.. (2014) Synthesis and Structure-Activity Relationship Studies of N-Benzyl-2-phenylpyrimidin-4-amine Derivatives as Potent USP1/UAF1 Deubiquitinase Inhibitors with Anticancer Activity against Nonsmall Cell Lung Cancer. J Med Chem, 57 (19): 8099-110. [PMID:25229643]

3. Ma A, Tang M, Zhang L, Wang B, Yang Z, Liu Y, Xu G, Wu L, Jing T, Xu X et al.. (2019) USP1 inhibition destabilizes KPNA2 and suppresses breast cancer metastasis. Oncogene, 38 (13): 2405-2419. [PMID:30531833]

4. Mistry H, Hsieh G, Buhrlage SJ, Huang M, Park E, Cuny GD, Galinsky I, Stone RM, Gray NS, D'Andrea AD et al.. (2013) Small-molecule inhibitors of USP1 target ID1 degradation in leukemic cells. Mol Cancer Ther, 12 (12): 2651-62. [PMID:24130053]

5. Tan L, Shan H, Han C, Zhang Z, Shen J, Zhang X, Xiang H, Lu K, Qi C, Li Y et al.. (2022) Discovery of Potent OTUB1/USP8 Dual Inhibitors Targeting Proteostasis in Non-Small-Cell Lung Cancer. J Med Chem, 65 (20): 13645-13659. [PMID:36221183]

6. Xu X, Li S, Cui X, Han K, Wang J, Hou X, Cui L, He S, Xiao J, Yang Y. (2019) Inhibition of Ubiquitin Specific Protease 1 Sensitizes Colorectal Cancer Cells to DNA-Damaging Chemotherapeutics. Front Oncol, 9: 1406. [PMID:31921663]

7. Zhao Y, Xue C, Xie Z, Ouyang X, Li L. (2020) Comprehensive analysis of ubiquitin-specific protease 1 reveals its importance in hepatocellular carcinoma. Cell Prolif, 53 (10): e12908. [PMID:32951278]

How to cite this page

C19: Ubiquitin-specific protease: ubiquitin specific peptidase 1. Last modified on 13/10/2022. Accessed on 14/06/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2428.