OSU-03012 is a novel and potent inhibitor of PDK-1. OSU-03012 exhibits anti-cancer activity in a COX-2-independent manner via inhibition of the phosphatidyl inositol-3-kinase (PI3K)/Akt pathway. It has an IC50 of 5 µM for inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1), and therefore Akt activation, with no measurable COX-2 inhibition up to 50 µM. OSU-03012 induces apoptosis of chronic lymphocytic leukemia (CLL) cells independent of bcl-2 overexpression using both caspase-dependent and independent pathways. A recent study shows that OSU-03012 could enhance the susceptibility of (Bcr)-Abl mutant cell lines to imatinib-induced apoptosis. OSU-03012 may lead to cell swelling and shortening of AP via reduced ATP production in mouse ventricular cells.
|Cell lines||VS and HMS-97 cells|
|Preparation method||Cell proliferation assay VS and HMS-97 cells were grown in polylysine/laminin-coated 96-well plates (5 × 103 to 1 × 104 per well). After incubation at 37°C for 24 hrs, cells were treated with various concentrations of OSU-03012 or DMSO as a vehicle control at 37°C for another 48 hrs. To assess cell proliferation, the CellTiter 96®AQueous One Solution Cell Proliferation Assay (Promega) was used according to the manufacturer’s instructions. Briefly, 20μl of CellTiter 96® AQueous One Solution Reagent were added to each well and incubated at 37°C for 1 to 4 hrs. The amount of colored formazan produced in the cells was measured at 490nm using a Victor3 1420 Multilabel Counter (Perkin Elmer). The percentage of cell proliferation was plotted against the concentrations of OSU-03012, and the IC50 (defined as the drug concentration at which the population of viable cells was reduced by 50%) was determined using CalcuSyn software (Biosoft). The experiments were replicated six times, and the mean IC50 was calculated.|
|Animal models||Schwannoma xenografts in severe combined immunodeficiency mice (SCID)|
|Formulation||methylcellulose (0.5%, w/v) and Tween 80 (0.1%, w/v) in sterile water|
|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 ≥90 mg/mL|
OSU-03012 suppresses GRP78/BiP expression that causes PERK-dependent increases in tumor cell killing.
Booth et al. Cancer Biol Ther. 2012 Feb 15;13(4):224-36. PMID: 22354011.
Endogenous adenosine contributes to renal sympathetic neurotransmission via postjunctional A1 receptor-mediated coincident signaling.
Jackson et al. Am J Physiol Renal Physiol. 2012 Feb;302(4):F466-76. PMID: 22114202.
The phosphoinositide-3-kinase-Akt signaling pathway is important for Staphylococcus aureus internalization by endothelial cells.
Oviedo-Boyso et al. Infect Immun. 2011 Nov;79(11):4569-77. PMID: 21844240.
OSU-03012, a novel celecoxib derivative, induces cell swelling and shortens action potential duration in mouse ventricular cells.
Yamamoto et al. Biomed Res. 2010 Dec;31(6):413-7. PMID: 21187652.
OSU-03012 enhances Ad.7-induced GBM cell killing via ER stress and autophagy and by decreasing expression of mitochondrial protective proteins.
Hamed et al. Cancer Biol Ther. 2010 Apr;9(7):526-36. PMID: 20107314.
|Related PDK1 Products|
NVP-BAG956 is a potent, ATP-competitive and selective dual PDK1 and class I PI 3-K inhibitor (IC50 values are 245, 56, 446, 35 and 117 nM for PDK1 and PI 3-K p110 -α, -β, -δ, and -γ respectively).
HS-173 is a potent PI3Kα inhibitor with IC50 of 0.8 nM.
BX912 is a selective potent PDK1 inhibitor with IC50 of 12 nM.
BX795 is a potent and specific TBK1, IKKε and PDK-1 inhibitor with IC50 of 6 nM, 41 nM and 111 nM, respectively.
GSK2334470 is a highly specific and potent inhibitor of PDK1 with IC50 of 10 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2017 AbMole BioScience. All Rights Reserved.