Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors
Abstract
1. Introduction
2. The Ubiquitylation System
2.1. The Ubiquitylation and Deubiquitylation Processes
2.2. Structural Characteristics of USPs
3. Roles of USPs in Cancers
4. Methods in Screening and Identification of Inhibitors for USPs
4.1. Activity-Based Probes
4.2. Ub-AMC
4.3. Ub-PLA2
4.4. TR-FRET
4.5. SDS-PAGE-Coomassie
4.6. MADAL-TOF
5. Recent Development of USP Inhibitors
5.1. USP Inhibitors in Clinical Trials
5.2. USP Inhibitors at Early Stage of Drug Discovery
5.2.1. USP1 Inhibitors
5.2.2. USP2 Inhibitors
5.2.3. USP2/4/5/7/8/15/20/28/47/UCHL1/UCHL3/UCHL5 Inhibitors
5.2.4. USP2/5/8/UCHL1/UCHL3 Inhibitors
5.2.5. USP2/7 Inhibitors
5.2.6. USP4/USP5 Inhibitors
5.2.7. USP5/7/8/13/14/15/22 Inhibitors
5.2.8. USP5/9X/14/24/UCHL5 Inhibitors
5.2.9. USP7 Inhibitors
5.2.10. USP7/8 Inhibitors
5.2.11. USP7/10 Inhibitors
5.2.12. USP7/47 Inhibitors
5.2.13. USP10/13 Inhibitors
5.2.14. USP11/15 Inhibitors
5.2.15. USP14 Inhibitors
5.2.16. USP14/UCLH5 Inhibitors
5.2.17. USP25/28 Inhibitors
5.2.18. USP30 Inhibitors
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Pathway | USPs Involved | Refs |
---|---|---|
DNA damage repair | USP1, USP28 | [35,36] |
TGF-β | USP2a, USP4, USP9X, USP15, USP26 | [34,37,38,39,40] |
Wnt/β-catenin | USP4, USP5, USP9X, USP14 | [41,42,43,44,45] |
p53 | USP2, USP4, USP5, USP7, USP10, USP15, USP24, USP42 | [31,32,33,46,47,48,49,50,51,52,53,54,55] |
c-Myc | USP2, USP10, USP22, USP28, USP36, USP37 | [56,57,58,59,60,61] |
Akt | USP4, USP12, USP14, USP22, USP46 | [62,63,64,65,66,67] |
JAKs-STATs | USP7 | [68] |
NF-κB | USP4, USP11, USP14, USP15, USP18, USP19, USP20, USP35, USP24, USP48 | [69,70,71,72,73,74,75,76,77,78,79,80,81,82] |
GPCR | USP4, USP8, USP14, USP20, USP30 | [83,84,85,86] |
Target | Compound ID | PDB | Refs |
---|---|---|---|
USP inhibitors in clinical trials | |||
USP14/UCHL5 | b-AP15 | None | [103] |
VLX1570 | None | [109] | |
USP inhibitors of reported new chemical entities | |||
USP1 | Pimozide | None | [113] |
GW7647 | None | ||
Trifluoperazine | None | ||
Rottlerin | None | ||
C527 | None | [114] | |
SJB2-043 | None | ||
SJB3-091A | None | ||
ML323 | None | [115,116] | |
USP2 | Q29 | None | [117] |
ML364 | None | [118] | |
LCAHA | None | [119] | |
STD1T | None | [120] | |
6TG | 5XU8 | [121] | |
USP2/4/5/7/8/15/20/28/47/UCHL1/UCHL3/UCHL5 | PR619 | None | [122,123] |
USP2/5/8/UCHL1/UCHL3 | AM416 | None | [124] |
RA9 | None | ||
RA14 | None | ||
USP2/7 | NSC632839 | None | [98] |
Compound 14 | None | [125] | |
USP4/5 | Vialinin A | None | [126] |
USP5/7/8/13/14/15/22 | Curcusone D | None | [127] |
USP5/9X/14/24/UCHL5 | WP1130 (Degrasny) | None | [128,129,130,131] |
EOAI3402143 (G9) | None | [132] | |
USP7 | HBX-41108 | None | [133] |
HBX-19818 | None | [134] | |
HBX-28258 | None | ||
Spongiacidin A | None | [135] | |
GEN-6640 | 5UQV | [136] | |
GEN-6776 | 5UQX | ||
XL188 | 5V6S | [137] | |
ALM2 | 5N9R | [138] | |
ALM45 | 6F5H | [139] | |
FT671 | 5NGE | [140,141] | |
FT827 | 5NGF | ||
Compound 2 | 5WHC | [142] | |
Compound 28 | None | ||
Parthenolide (PTL) | None | [143] | |
Costunolide | None | ||
α-santonin | None | ||
USP7/8 | HY50736 | None | [144] |
HY50737A | None | ||
USP7/10 | Compound 3 | None | [145] |
Compound 9 | None | ||
USP7/47 | P22077 | None | [122,146,147] |
P5091 | None | [148,149,150] | |
P50429 | None | [151] | |
USP10/13 | Spautin-1 | None | [152] |
USP11/15 | Mitoxantrone | 6GH9 | [153,154] |
USP14 | IU1 | 6IIK | [155] |
IU1-47 | 6IIL | [156,157] | |
IU1-206 | 6IIM | [157] | |
IU1-248 | 6IIN | [157] | |
USP14/UCHL5 | Auranofin | None | [158,159] |
CuPT | None | [160,161] | |
PtPT | None | [162] | |
NiPT | None | [163] | |
USP25/28 | AZ1 | None | [164] |
USP30 | MF-094 | None | [165] |
15-oxospiramilactone (S3) | None | [166] |
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Chen, S.; Liu, Y.; Zhou, H. Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors. Int. J. Mol. Sci. 2021, 22, 4546. https://doi.org/10.3390/ijms22094546
Chen S, Liu Y, Zhou H. Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors. International Journal of Molecular Sciences. 2021; 22(9):4546. https://doi.org/10.3390/ijms22094546
Chicago/Turabian StyleChen, Shiyao, Yunqi Liu, and Huchen Zhou. 2021. "Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors" International Journal of Molecular Sciences 22, no. 9: 4546. https://doi.org/10.3390/ijms22094546
APA StyleChen, S., Liu, Y., & Zhou, H. (2021). Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors. International Journal of Molecular Sciences, 22(9), 4546. https://doi.org/10.3390/ijms22094546