OSU-03012 (AR-12) - Moligand™, 10mM in DMSO , 3-phosphoinositide dependent protein kinase-1 inhibitor, CAS No.742112-33-0, 3-phosphoinositide dependent protein kinase-1 inhibitor

CAS: 742112-33-0 Cat. No.: O407997 Molecular Weight: 460.46

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

2-amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

OSU-03012 (AR-12) OSU-03012 (AR-12) is a potent inhibitor of recombinant PDK-1(phosphoinositide-dependent kinase 1) with IC50 of 5 μM in a cell-free assay and 2-fold increase in potency over OSU-02067.
In vitro

OSU-03012 induces apoptotic death in PC-3 cells with IC50 of 5 µM and reduces the activity of immunoprecipitated p70^S6K. OSU-03012 completely suppress cell growth in a diverse range of tumor cell lines at concentrations of 3–5 μm, as compared with the concentration of at least 50 μm required for celecoxib. OSU-03012 promotes cell killing to a greater extent in glioma cells than in nontransformed astrocytes. OSU-03012 causes a dose-dependent induction of cell death that is not altered by p53 mutation, expression of ERBB1 VIII, or loss of phosphatase and tensin function due to a homolog deletion on chromosome 10. OSU-03012 and ionizing radiation cause an additive, caspase-independent elevation in cell killing. OSU-03012 lethality as a single agent or when combined with signaling modulators is not modified in cells lacking expression of BIM or of BAX/BAK. OSU-03012 promotes the release of cathepsin B from the lysosomal compartment and that of AIF from mitochondria. The lethality of OSU-03012 is attenuated in protein kinase R-like endoplasmic reticulum kinase-/- cells, which correlated with the reduced cleavage of BID and suppression of cathepsin B and AIF release into the cytosol. OSU-03012 inhibits thyroid cancer cell (NPA, WRO, and ARO cells) proliferation, migration and induces apoptosis, which results in an increase of cells in the S phase without an increase of cells in G2. OSU-03012 is an ATP-competitive inhibitor of PAK activity and suppresses the phosphorylation of AKT in thyroid cancer cells. OSU-03012 inhibits cell growth of hepatocellular carcinoma cell lines including Huh7, Hep3B and HepG2 cells with IC50 values below 1 μM. OSU-03012 does not suppress PDK1 or AKT activity or induce cellular apoptosis but induces autophagy in Huh7 cells. Moreover, accumulation of reactive oxygen species (ROS) is detected after OSU-03012 treatment. A recent study shows that OSU-03012 could enhance the susceptibility of (Bcr)-Abl mutant cell lines to imatinib-induced apoptosis.

In vivo

OSU-03012 suppresses tumor growth by 57.59% and increases cleaved LC3 in Huh7 tumor xenografts at 200 mg/kg. OSU-03012 remarkably decreases expression of EGFR protein in the tumors by 48% compared with vehicle controls and also prevents YB-1 from binding to the EGFR promoter in MDA-MB-435/LCC6 xenografts. OSU-03012 is well tolerated and inhibits the growth of HMS-97 schwannoma xenografts by 55% after oral administration.
Cell Data

cell lines：primary human monocyte-derived macrophages

Concentrations：0-10 μM

Incubation Time：~72 hours

Powder Purity:≥98%

Specifications

Synonyms

2-amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

OSU-03012 (AR-12) is a potent inhibitor of recombinant PDK-1(phosphoinositide-dependent kinase 1) with IC50 of 5 μM in a cell-free assay and 2-fold increase in potency over OSU-02067.

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

3-phosphoinositide dependent protein kinase-1 inhibitor

Product Properties

• ALogP: 5.2

Names and Identifiers

• Isomeric SMILES: C1=CC=C2C(=C1)C=CC3=C2C=CC(=C3)C4=CC(=NN4C5=CC=C(C=C5)NC(=O)CN)C(F)(F)F
• Molecular Weight: 460.46
• Reaxy-Rn: 11001693
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=11001693&ln=

Associated Targets(Human)

PDPK1 Tchem 3-phosphoinositide-dependent protein kinase 1 (1 Activities)

Discover Target: PDPK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Melt Point(°C): 177-180°C