TG-6304 (TG6304) is a first-in-class, potent, highly selective, cell-permeable DCN3 inhibitor with Ki of 35 nM, does not bind to DCN1 at 30 uM.TC-6304 engages DCN3 in cells in a dose-dependent manner but does not affect the neddylation of any of the cullins.TC-6304 effectively enhances the thermal stability of cellular DCN3 protein in a dose-dependent manner and has no significant effect on the thermal stability of cellular DCN1 protein (10-1000 nM).

UbcH5c inhibitor DHPO is a small molecule UbcH5c inhibitor, directly targets UbcH5c with KD of 37.5 uM.DHPO effectively engaged by the UbcH5c protein in both Panc1 and SW1990 cells.DHPO exerts significant growth inhibition in pancreatic cancer cells in vitro (IC50=2.3-8.5 uM), prevents the migration and invasion of both Panc1 and SW1990 cells.DHPO inhibits pancreatic cancer cell growth and metastasis by inhibiting the NF-κB pathway.DHPO suppresses orthotopic pancreatic tumor growth in vivo, without causing significant host toxicity.DHPO prevents metastasis of pancreatic cancer in vivo.

UC-764864 (UC764864) is a small-molecule inhibitor that targeted ubiquitin-conjugating enzyme UBE2N active site.UC-764864 blocks ubiquitination of innate immune- and inflammatory-related substrates in human AML cell lines.Inhibition of UBE2N function disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing normal HSPCs in vitro.

UC-764865 (UC764865) is a small-molecule inhibitor that targeted ubiquitin-conjugating enzyme UBE2N active site.UC-764865 blocks ubiquitination of innate immune- and inflammatory-related substrates in human AML cell lines.Inhibition of UBE2N function disrupted oncogenic immune signaling by promoting cell death of leukemic HSPCs while sparing normal HSPCs in vitro.

UCHL1 inhibitor 27 is a potent, selective, covalent UCHL1 inhibitor with IC50 of 90 nM.UCHL1 inhibitor 27 demonstrated exquisite selectivity in a cross-screening against 20 DUBs.UCHL1 inhibitor 27 demonstrated >50% fibroblast–myofibroblast transition (FMT) inhibition (IC50=100 nM) in idiopathic pulmonary fibrosis (IPF), as well as αSMA inhibition.UCHL1 inhibitor 27 is a powerful and selective probe to explore UCHL1 activity with potential application to substrate identification, mode of action studies, and cellular target profiling.

USP inhibitor 1 is an irreversible USP inhibitor with submicromolar IC50 of USP4 and its phylogenetic relative USP11, also functionally inhibits USP33, leading to CP110 instability and synergy with ATR inhibition in U2OS cells.

USP inhibitor 2 is a broad DUB inhibitor with IC50 of 0.04 and 0.21 uM for USP4 and USP11, also inhibits USP10/16/15/19 with submicromolar potency, forms a covalent adduct with USP11. USP inhibitor 2 does not inhibit USP5 (IC50>100 uM).

USP10 inhibitor Wu-5 (Wu-5) is a novel small molecule USP10 inhibitor inducing the degradation of FLT3-mutated protein, directly interacts and inactivates USP10, the deubiquitinase for FLT3-ITD in vitro (IC50=8.3 uM) and in FLT3-ITD-positive AML cells.Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 uM, respectively.Wu-5 (1-10 μM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD.Combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins.

USP30 inhibitor Q14 peptide is a peptide derived from the transmembrane (TM) domain of USP30 that can target mitochondrial-anchored USP30 directly and increase mitophagy.

USP30Inh-1 is a potent, selective small molecule USP30 inhibitor with IC50 of 15-30 nM (inhibition of USP30-mediated cleavage of Ub-Rho110).USP30Inh-1 is anticipated to form a covalent linkage with the catalytic cysteine within the USP30 active site.USP30Inh-1 demonstrated good selectivity against >40 known DUB enzymes at 1 uM. USP30Inh-1 (1-10 uM) enhances mitoKeima signal in SHSY5Y cell, increases p-Ser65-Ub in dopaminergic neurones and astrocytes, as well as in Parkin heterozygote fibroblasts.

USP5 inhibitor 64 is a selective chemical probe (inhibitor) against USP5 deubiquitinase, binds to the USP5 ZnF-UBD (zinc-finger ubiquitin binding domain) with KD of 2.8 uM.USP5 inhibitor 64 is selective over nine proteins containing structurally similar ZnF-UBD domains.USP5 inhibitor 64 inhibits the USP5 catalytic cleavage of a di-ubiquitin substrate in an in vitro assay.

USP7-866 is a novel potent selective inhibitor of USP7 with IC50 of 0.18 nM; USP7-866 inhibited the growth of p53-mutant small cell lung cancer cell line H526 at a CC50 of 42 nM.

EC144 is a potent and selective inhibitor of heat shock protein 90 (Hsp90) with an IC50 of 1.1 nM. EC144 inhibits tumor growth and causes partial tumor regressions. EC144 has the potential for the research of cancer diseases.

FT709 is a potent and selective USP9X inhibitor, an IC50 of 82 nM. USP9X has been linked with centrosome function, chromosome alignment during mitosis, EGF receptor degradation, chemo-sensitization, and circadian rhythms.

MG-262 is a reversible proteasome inhibitor with diverse biological activities.

Macbecin is a stable HSP90 inhibitor by binding to the ATP-binding site with an IC50 of 2 μM and a Kd of 0.24 μM. Macbecin exhibits antitumor and cytocidal activities.

Suc-Gly-Gly-Phe-pNA is the chymotrypsin substrate with an Km value of 1.6 mM.

Iu1-248, a derivative of IU1, is a potent and selective ubiquitin specific peptidase 14 (USP14) inhibitor with an IC50 of 0.83 μM.

20S Proteasome activator 1 is a potent 20S proteasome activator with EC200 values of 0.3 μM, 0.7 μM and 1.8 μM for trypsin-like site, chymotrypsin-like site and caspase-like site. 20S Proteasome activator 1 translates well in a cellular system, preventing the accumulation of the pathogenic A53T mutant of α-synuclein. 20S Proteasome activator 1 can be used for researching neurodegenerative diseases.

Ac-PAL-AMC is a fluorogenic substrate specific for 20S proteasome LMP2/β1i activity.

Ac-WLA-AMC is a specific 20S constitutive proteasome β5 fluorogenic substrate.

NIC-0102 is an orally active proteasome inhibitor (pIC50=7.55) that specifically inhibits NLRP3 inflammatory vesicle activation. NIC-0102 shows potent anti-inflammatory effects in a model of dextran sulfate sodium (DSS)-induced ulcerative colitis. NIC-0102 also inhibits production of pro-IL-1β.