742112-33-0

Basic information

• Product Name: OSU-03012
• Synonyms: OSU-03012;2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]acetamide;N/AAR-12;OSU-03012 (AR-12);AR-12;2-amino-N-(4-(5-(phenanthren-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)acetamide;2-Amino-N-[4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl]acetamide OSU-03012;OSU-03012, >=98%
• CAS NO: 742112-33-0
• Molecular Formula: C26H19F3N4O
• Molecular Weight: 460.46
• EINECS: -0
• Product Categories: Inhibitor of phosphoinositide-dependent kinase-1.;Inhibitors;Akt;mTOR;PI3K
• Mol File: 742112-33-0.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 683.017 °C at 760 mmHg
• Flash Point: 366.876 °C
• Appearance: /
• Density: 1.369 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.649
• Solubility: ≥23 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• CAS DataBase Reference: OSU-03012(CAS DataBase Reference)
• NIST Chemistry Reference: OSU-03012(742112-33-0)
• EPA Substance Registry System: OSU-03012(742112-33-0)

Safety Data

• Hazardous Substances Data: 742112-33-0(Hazardous Substances Data)

Usage

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. 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. 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. 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. It does not inhibit signal transduction through the mitogen-activated protein kinase (MAPK) pathway. OSU03012 induces apoptosis of chronic lymphocytic leukemia cells independent of bcl-2 overexpression using both caspase-dependent and independent pathways.

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.

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.

InChI:InChI=1/C26H19F3N4O/c27-26(28,29)24-14-23(33(32-24)20-10-8-19(9-11-20)31-25(34)15-30)18-7-12-22-17(13-18)6-5-16-3-1-2-4-21(16)22/h1-14H,15,30H2,(H,31,34)

Upstream product

• 100-16-3 4-nitrophenylhydrazone 
• 15389-33-0 4,4,4-Trifluoro-1-phenanthren-2-yl-butane-1,3-dione 
• 5960-69-0 2-acetylphenanthrene 
• 1100051-52-2 C₂₄H₁₄F₃N₃O₂ 
• 882854-64-0 4-(5-phenanthren-2-yl-3-trifluoromethyl-pyrazol-1-yl)-phenylamine 
• 1092540-88-9 C₃₁H₂₇F₃N₄O₃ 

Relevant articles and documents

Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA.

PDK-1/AKT SIGNALING INHIBITORS

A new class of phosphoinositide-dependent kinase-1 (PDK-1) inhibitors of formula (I): wherein X is selected from the group consisting of alkyl and haloalkyl; Ar is an aryl radical selected from the group consisting of phenyl, biphenyl, naphthyl, anthryl,