|S2243||Degrasyn (WP1130)||<1 mg/mL||77 mg/mL||18 mg/mL|
|S7130||PR-619||<1 mg/mL||45 mg/mL||<1 mg/mL|
|S7132||P5091 (P005091)||<1 mg/mL||28 mg/mL||<1 mg/mL|
|S7134||IU1||<1 mg/mL||60 mg/mL||60 mg/mL|
|S7135||LDN-57444||<1 mg/mL||11 mg/mL||<1 mg/mL|
|S8288||VLX1570||<1 mg/mL||93 mg/mL||<1 mg/mL|
|S7140||TCID||<1 mg/mL||23 mg/mL||<1 mg/mL|
|S7133||P22077||<1 mg/mL||63 mg/mL||<1 mg/mL|
|S4920||b-AP15||<1 mg/mL||48 mg/mL||<1 mg/mL|
|S7529||ML323||<1 mg/mL||76 mg/mL||38 mg/mL|
Degrasyn (WP1130) is a selective deubiquitinase (DUB: USP5, UCH-L1, USP9x, USP14, and UCH37) inhibitor and also suppresses Bcr/Abl, also a JAK2 transducer (without affecting 20S proteasome) and activator of transcription (STAT).
HEK-293 cells expressing Strep-CLASPIN were first arrested in S-phase with HU or in mitosis with nocodazole. Cycloheximide was then added to prevent further protein synthesis in the presence or absence of the USP9X inhibitor WP1130 and samples were harvested at the indicated times. A sample from the same cell line uninduced (U) was loaded as control.
PR-619 is a non-selective, reversible inhibitor of the deubiquitinylating enzymes (DUBs) with EC50 of 1-20 μM in a cell-free assay.
P5091(P005091) is a selective and potent inhibitor of ubiquitin-specific protease 7 (USP7) with EC50 of 4.2 μM and the closely related USP47.
(e) MM.1S cells were treated with RRx-001 (1.25 μM), P5091 (3 μM) or RRx-001 plus P5091 for 12 h; protein extracts were analyzed for total DNMT activity using the EpiQuik DNMT activity kit (mean±s.d.; P<0.001; n=3). (f) MM.1S cells were treated with RRx-001 (1.25 μM), P5091 (3 μM) or RRx-001 plus P5091 for 12 h; protein lysates were then subjected to immunoblot analysis using antibodies specific against p21, HDM2, p53 or GAPDH.
IU1 is a cell-permeable, reversible and selective proteasome inhibitor of human USP14 with IC50 of 4.7 μ M, 25-fold selective to IsoT.
LDN-57444 is a reversible, competitive proteasome inhibitor for Uch-L1 with IC50 of 0.88 μM, 28-fold selectivity over isoform Uch-L3.
Representative results of Western blot showed the effects of LDN (10.0 μM) treatments on the expressions of LC3-II and LC3-I from Normoxia and OGD groups of cPKCc+/+ and cPKCc/ cortical neurons (n = 6 per group).
VLX1570 is a competitive inhibitor of proteasome DUB activity, with an IC50 of ~10 μM in vitro.
TCID is a DUB inhibitor for ubiquitin C-terminal hydrolase L3 with IC50 of 0.6 μM, 125-fold selective to L1.
P22077 is an inhibitor of ubiquitin-specific protease USP7 with EC50 of 8.6 μM, also inhibits the closely related USP47.
b-AP15 is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM.
A USP14 inhibitor directly inhibits OSCC cell proliferation and triggers apoptosis. (A-D) OSCC cells were treated with indicated doses of b-AP15 for 24 h. (A) Cell proliferation was monitored by CCK8 assay. b-AP15 dramatically decreased cancer cells viability in a dose-dependent manner (p < 0.01). All values represented means ± SD of three independent experiments and each was performed in triplicate. (B, C) Flow cytometry analysis indicated that b-AP15 triggered significant apoptosis of OSCC cells (p < 0.01). Data were obtained in more than three independent experiments. (D) Apoptosis-related proteins were examined by western blot analysis. Inhibition of USP14 with b-AP15 induced a massive increase of ubiquitinated proteins, which then triggered apoptosis of cancer cells, activating caspase 3 to induce cleavage of caspase 3 and PARP.
ML323 displays reversible, nanomolar inhibitory activity and excellent selectivity toward USP1/UAF1 with IC50 of 76 nM.