IU1 is an inhibitor of USP14, a deubiquitinating enzyme associated with the proteasome. The proteasome mediates the cellular degradation of oxidized, damaged and misfolded proteins which, if not removed, accumulate and become toxic to cells. USP14 is one of several deubiquitinating enzymes (DUBs) responsible for shortening proteasome-bound ubiquitin chains, which is known to antagonize the degradation of ubiquitin-protein conjugates. IU1 inhibits the catalytic activity of proteasome-associated Usp14 in vitro (IC50 < 4 μM). IU1 selectively stimulates ubiquitin-dependent protein degradation in vitro at 34 μM and in MEF cells at 50 μM. At 75 μM, IU1 reduces accumulation of oxidized proteins in HEK293 cells, alleviating cytotoxicity induced by oxidative stress. IU1 may help to eliminate toxic proteins more effectively by enhancing their degradation.
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Enhancement of proteasome activity by a small-molecule inhibitor of USP14.
Lee BH, et al. Nature. 2010 Sep 9;467(7312):179-84. PMID: 20829789.
Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes.
Lee MJ, et al. Mol Cell Proteomics. 2011 May;10(5):R110.003871. PMID: 20823120.
|Related Proteasome Products|
|Sivelestat sodium tetrahydrate
Sivelestat sodium tetrahydrate is a competitive inhibitor of human neutrophil elastase, also inhibits leukocyte elastase obtained from rabbit, rat, hamster and mouse.
MG-101 is a potent inhibitor of cysteine proteases including calpain I (Ki = 190 nM), calpain II (Ki = 220 nM), cathepsin B (Ki = 150 nM), and cathepsin L (Ki = 500 pM). IC50 value: 150 nM (Ki)
VR23 is a small molecule that potently inhibited the activities of trypsin-like proteasomes (IC50 = 1 nM), chymotrypsin-like proteasomes (IC50 = 50-100 nM), and caspase-like proteasomes (IC50 = 3 μM).
Gabexate Mesylate is a serine protease inhibitor with IC50 of 0.19 μM which is used therapeutically in the treatment of pancreatitis and disseminated intravascular coagulation.
CEP-18770 is an orally active inhibitor of the chymotrypsin-like activity of proteasome with IC50 of 3.8 nM, with only marginal inhibition of the tryptic and peptidylglutamyl activities of the proteosome.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.