| Identification | Back Directory | [Name]
OSU-03012 | [CAS]
742112-33-0 | [Synonyms]
AR-12
CS-1848
N/AAR-12
OSU-03012
OSU-03012, >=98%
OSU-03012 (AR-12)
OSU-03012 USP/EP/BP
N/AAR-12; OSU03012; OSU 03012
OSU-03012 (AR-12);N/AAR-12; OSU03012; OSU 03012
2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]acetamide
2-amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide
Acetamide, 2-amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]-
2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]acetamide OSU-03012 | [Molecular Formula]
C26H19F3N4O | [MDL Number]
MFCD12912272 | [MOL File]
742112-33-0.mol | [Molecular Weight]
460.46 |
| Hazard Information | Back Directory | [Description]
Cyclooxygenase-2 (COX-2) appears to play a significant role in the development and progression of cancer and COX-2 inhibitors such as celecoxib exhibit anti-cancer activity.1 OSU03012 is an analog of celecoxib that exhibits anti-cancer activity in a COX-2-independent manner via inhibition of the phosphatidyl inositol-3-kinase/Akt pathway.2,3,4 It has an IC50 value of 5 μM for inhibition of 3-phosphoinositide-dependent kinase-1, and therefore Akt activation, with no measurable COX-2 inhibition up to 50 μM.3 OSU03012 is a potent inhibitor of tumor cell growth with an average inhibitory concentration of 1.1 μM across a panel of 60 cancer cell lines.3 It does not inhibit signal transduction through the mitogen-activated protein kinase (MAPK) pathway.4 OSU03012 induces apoptosis of chronic lymphocytic leukemia cells independent of bcl-2 overexpression using both caspase-dependent and independent pathways.2 | [Uses]
OSU 03012 is a PDK1 inhibitor and inducer of caspase and p53-independent apoptosis, also used in the development of anticancer agents by modification of novel immunosuppressant FTY720 and PDK1 inhibitor OSU-03012, compound for treating Alzheimers diseases. | [Definition]
ChEBI: A member of the class of pyrazoles that is N-[4-(pyrazol-1-yl)phenyl]glycinamide in which the pyrazole ring is substituted at positions 3 and 5 by trifluoromethyl and phenanthrene-2-yl groups respectively. | [Enzyme inhibitor]
This PDK1 inhibitor (FW = 460.45 g/mol; CAS 742112-33-0; Soluble to
100 mM in DMSO), systematically named 2-Amino-N-[4-[5- (2-
phenanthrenyl) -3- (trifluoromethyl) -1H-pyrazol-1-yl]phenyl]acetamide,
blocks Akt signaling by targeting 3-Phosphoinositide-Dependent Protein
Kinase-1 (IC50 = 2-3 μM). Exposure of PC-3 cells to this agent leads to
Akt dephosphorylation and inhibition of p70 S6 kinase activity. OSU-
03012 promotes glioma cell killing that is dependent on endoplasmic
reticulum stress, lysosomal dysfunction, and BID-dependent release of AIF
from mitochondria, and whose lethality is enhanced by irradiation or by
inhibition of protective signaling pathways. OSU03012 induced
mitochondrial-dependent apoptosis of medulloblastoma cells and enhanced
the cytotoxic effects of chemotherapeutic drugs in a synergistic or additive
manner When tested in vivo, OSU03012 inhibits the growth of
established medulloblastoma xenograft tumors in a dose-dependent manner
and augmented the antitumor effects of mammalian target of rapamycin
inhibitor CCI-779. | [storage]
Store at -20°C | [References]
[1] zhu j1, huang jw, tseng ph, yang yt, fowble j, shiau cw, shaw yj, kulp sk, chen cs. from the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. cancer res. 2004 jun 15;64(12):4309-18.
[2] lee tx1, packer md, huang j, akhmametyeva em, kulp sk, chen cs, giovannini m, jacob a, welling db, chang ls. growth inhibitory and anti-tumour activities of osu-03012, a novel pdk-1 inhibitor, on vestibular schwannoma and malignant schwannoma cells. eur j cancer. 2009 jun;45(9):1709-20. |
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