Oprozomib (ONX 0912, PR-047) is an orally bioavailable and selective proteasome inhibitor. Oprozomib (ONX 0912) selectively inhibited CT-L activity of both the constitutive proteasome (beta5) and immunoproteasome (LMP7) and demonstrated an absolute bioavailability of up to 39% in rodents and dogs. Oprozomib inhibits growth and induces apoptosis in MM cells resistant to conventional and bortezomib therapies. The anti-MM activity of Oprozomib (ONX 0912) is associated with activation of caspase-8, caspase-9, caspase-3, and poly(ADP) ribose polymerase, as well as inhibition of migration of MM cells and angiogenesis. Oprozomib significantly reduced tumor progression and prolonged survival in animal tumor model studies. Immununostaining of MM tumors from ONX 0912-treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Finally, Oprozomib (ONX 0912) enhances anti-MM activity of bortezomib, lenalidomide dexamethasone, or pan-histone deacetylase inhibitor.
|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.
|Solubility||DMSO 100 mg/mL|
A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma.
Chauhan D, et al. Blood. 2010 Dec 2;116(23):4906-15. PMID: 20805366.
Design and synthesis of an orally bioavailable and selective peptide epoxyketone proteasome inhibitor (PR-047).
Zhou HJ, et al. J Med Chem. 2009 May 14;52(9):3028-38. PMID: 19348473.
|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.