A review of drug discovery opportunities across deubiquitylating (DUB) enzymes
Harrigan et al. (2018) Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov (1):57-78. doi: 10.1038/nrd.2017.152. Epub 2017 Sep 29.
Arguing the value of target class focussed drug discovery; building a target class-specific assay and chemistry platform
Barnash et al. (2017) Target class drug discovery. Nat Chem Biol. 13(10):1053-1056. doi: 10.1038/nchembio.2473.
DUB targeting small molecule drug discovery by Genentech
Di Lello et al. (2017) Discovery of Small-Molecule Inhibitors of Ubiquitin Specific Protease 7 (USP7) Using Integrated NMR and in Silico Techniques. J Med Chem. 60(24):10056-10070. doi: 10.1021/acs.jmedchem.7b01293. Epub 2017 Dec 8.
The application of Ubiquigent’s DUBprofiler™ service in DUB targeting small molecule drug discovery by Almac Discovery
Gavory et al. (2017) Discovery and characterization of highly potent and selective allosteric USP7 inhibitors. Nat Chem Biol. doi: 10.1038/nchembio.2528. [Epub ahead of print]
DUB targeting small molecule drug discovery by Genentech
Kategaya et al. (2017) USP7 small-molecule inhibitors interfere with ubiquitin binding. Nature. 550(7677):534-538. doi: 10.1038/nature24006. Epub 2017 Oct 18.
The application of Ubiquigent’s DUBprofiler™ service in DUB targeting small molecule drug discovery by the Dana-Farber Cancer Institute and Harvard Medical School
Lamberto et al. (2017) Structure-Guided Development of a Potent and Selective Non-covalent Active-Site Inhibitor of USP7. Cell Chem Biol. pii: S2451-9456(17)30329-X. doi: 10.1016/j.chembiol.2017.09.003. [Epub ahead of print]
DUB targeting small molecule drug discovery by Progenra, University of Connecticut and Yale University
Pozhidaeva et al. (2017) USP7-Specific Inhibitors Target and Modify the Enzyme's Active Site via Distinct Chemical Mechanisms. Cell Chem Biol. pii: S2451-9456(17)30330-6. doi: 10.1016/j.chembiol.2017.09.004. [Epub ahead of print]
The application of Ubiquigent’s DUBprofiler™ service in DUB targeting small molecule drug discovery by FORMA Therapeutics
Turnbull et al. (2017) Molecular basis of USP7 inhibition by selective small-molecule inhibitors. Nature. 550(7677):481-486. doi: 10.1038/nature24451. Epub 2017 Oct 18.
The application of Ubiquigent’s DUBprofiler™ service in DUB targeting small molecule drug discovery by Almac Discovery and Astra Zeneca
Wrigley et al. (2017) Identification and characterisation of dual inhibitors of the USP25/28 Deubiquitinating enzyme subfamily. ACS Chem Biol DOI: 10.1021/acschembio.7b00334
The DUB USP5 as a potential target for inflammatory and neuropathic pain.
Gadotti et al. (2015) Small organic molecule disruptors of Cav3.2 - USP5 interactions reverse inflammatory and neuropathic pain. Mol Pain. 11. doi: 10.1186/s12990-015-0011-8. Epub 2015 Mar 14.
VM1, Caballero AG, Berger ND, Gladding CM, Chen L, Pfeifer TA, Zamponi GW.
Seminal paper associating the targeting of USP30 to the regulation of parkin-mediated mitophagy in the context of Parkinson’s disease
Bingol et al. (2014) The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 510(7505):370-5. doi: 10.1038/nature13418. Epub 2014 Jun 4.
Discussion paper by Ubiquigent’s Scientific Director and Chairman addressing the need for targeted chemical libraries to enable ubiquitin system drug discovery
Brown and Treherne (2014 ) Targeted chemical libraries: the keys to unlock the ubiquitin system Is novel chemistry the final frontier for ubiquitin system drug discovery? Drug Discovery World 66-74
A review of drug targeting opportunities across the ubiquitin system
Bedford, L., et al. (2012) Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat. Rev. Drug Disc. 10, 1-19.
The elucidation of the mechanics of the lysosomal and ubiquitin proteasome systems
Ciechanover, A. (2012) Intracellular protein degradation: From a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Biochim Biophys Acta 1824(1): 3-13.
Small molecule targeting of the immuno- and constitutive proteasome
Huber and Groll (2012) Inhibitors for the Immuno- and Constitutive Proteasome: Current and Future Trends in Drug Development. Angew Chem Int Ed Engl. doi: 10.1002/anie.201201616. [Epub ahead of print]
Therapeutic opportunities provided by the targeting of autophagy
Rubinsztein et al. (2012) Autophagy modulation as a potential therapeutic target for diverse diseases. Nat Rev Drug Discov 11(9), 709-730.
Small molecule E1 inhibitors
Ungermannova et al. (2012) Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (e1). PLoS One7, e29208.
A review of ubiquitin-like proteins
van der Veen and Ploegh (2012) Ubiquitin-Like Proteins. Annu Rev Biochem 81, 323-357.
Kinases and the ubiquitin system: A comparative review of drug discovery opportunities by Ubiquigent’s SAB Chairman
Cohen, P. and M. Tcherpakov (2010) Will the ubiquitin system furnish as many drug targets as protein kinases? Cell 143(5): 686-693. Uploaded: 13 February 2012
The E3 ubiquitin ligase IDOL regulates cellular LDL uptake: See Ubiquigent’s high-throughput small molecule IDOL screening assay
Zelcer et al. (2009) LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. Science 325(5936), 100-104.
