| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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Purity: ≥98%
| Targets |
PDK-1 (IC50 = 5 μM)
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|---|---|
| ln Vitro |
OSU-03012 induces apoptotic death in PC-3 cells with IC50 of 5 µM and reduces the activity of immunoprecipitated p70S6K. OSU-03012 completely inhibits cell growth in a variety of tumor cell lines at concentrations as low as 3-5 m, versus the concentration of at least 50 m needed for celecoxib.[1] Compared to untransformed astrocytes, OSU-03012 more strongly encourages cell killing in glioma cells. OSU-03012 induces cell death in a dose-dependent manner that is unaffected by the p53 mutation, the expression of ERBB1 VIII, or the loss of phosphatase and tensin function brought on by a homolog deletion on chromosome 10. Ionizing radiation and OSU-03012 increase cell death in an additive, caspase-independent manner. 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 encourages the release of cathepsin B from the lysosomal compartment and AIF from the mitochondria. In protein kinase R-like endoplasmic reticulum kinase-/- cells, the lethality of OSU-03012 is reduced, which is correlated with decreased BID cleavage and reduced cathepsin B and AIF release into the cytosol. [2] OSU-03012 inhibits the growth, migration, and apoptosis of thyroid cancer cells (NPA, WRO, and ARO cells), which causes a rise in S phase cells without a rise in G2 cells. OSU-03012 is an ATP-competitive inhibitor of PAK activity that prevents thyroid cancer cells from phosphorylating AKT. [3] With IC50 values under 1 M, OSU-03012 inhibits the growth of Huh7, Hep3B, and HepG2 cell lines, which are used to study hepatocellular carcinoma. In Huh7 cells, OSU-03012 induces autophagy but does not suppress PDK1 or AKT activity or cause cellular apoptosis. After OSU-03012 treatment, accumulation of reactive oxygen species (ROS) is also found. [4] According to a recent study, OSU-03012 may make (Bcr)-Abl mutant cell lines more susceptible to apoptosis caused by imatinib. [5]
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| ln Vivo |
OSU-03012 suppresses tumor growth by 57.59% and increases cleaved LC3 in Huh7 tumor xenografts at 200 mg/kg. [4] OSU-03012 significantly reduces EGFR protein expression in tumors by 48% when compared to vehicle controls and inhibits YB-1 from binding to the EGFR promoter in MDA-MB-435/LCC6 xenografts. [6] The oral administration of OSU-03012 results in a 55% growth inhibition of HMS-97 schwannoma xenografts and is well tolerated. [7]
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| Enzyme Assay |
A PDK-1 kinase assay kit is used in this in vitro test. This cell-free assay is based on recombinant PDK-1's capacity to activate its downstream serum- and glucocorticoid-regulated kinase in the presence of DMSO vehicle or OSU-03012, which in turn phosphorylates the Akt/serum- and glucocorticoid-regulated kinase-specific peptide substrate RPRAATF with [γ-32P]ATP. Using P81 phosphocellulose paper and three washes with 0.75% phosphoric acid, the 32P-phosphorylated peptide substrate is then separated from the remaining [γ-32P]-ATP. The quantity is then measured in a scintillation counter.
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| Cell Assay |
The effect of OSU-03012 on PC-3 cell viability is assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay in six replicates. In 96-well, flat-bottomed plates, cells are grown for 24 hours in RPMI 1640 with 10% FBS supplement. They are exposed to different concentrations of OSU-03012 (0-10 μM) dissolved in DMSO (final concentration≤0.1%) in 1% serum–containing RPMI 1640 for various lengths of time (–72 hours). At a level comparable to that in OSU-03012-treated cells, controls are given DMSO vehicle. In place of the medium, 200 L of 0.5 mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide in 10% FBS-containing RPMI 1640 are added. The cells are incubated for two hours at 37 °C in the CO2 incubator. The reduced 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye is solubilized in 200 L DMSO per well after the supernatants are removed from the wells. Absorbance at 570 nm is determined by using a plate reader.
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| Animal Protocol |
Mice[3]
SCID/Rag2m mice (6-8 weeks old, female) are subcutaneously injected with 1×107 MDA-MB-435/LCC6 cells stably transfected with HER-2/neu. The right and left sides of the lower back of each mouse are injected with the cells. We inject two tumors into each of the eight mice. The mice are randomly divided into the vehicle, 0.5% methyl cellulose/0.1% Tween 80, or OSU-03012 groups after six weeks. The vehicle or OSU-03012 are administered orally to mice once daily for three days. On the fourth day of the experiment, mice are killed, the tumors are removed, and chromatin immunoprecipitation (ChIP) and protein isolations are performed on the tumors. |
| References | |
| Additional Infomation |
OSU-03012 is 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. It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor, an antineoplastic agent and an apoptosis inducer. It is a member of pyrazoles, a member of phenanthrenes, an organofluorine compound, a glycine derivative, an aromatic amide and an antibiotic antifungal drug.
PDK1 Inhibitor AR-12 is an orally bioavailable, small-molecule, celecoxib-derived inhibitor of phosphoinositide-dependent kinase-1 (PDK1) with potential antineoplastic activity. Devoid of any COX inhibiting activity, PDK1 inhibitor AR-12 binds to and inhibits the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1).; subsequently, the phosphorylation and activation of the serine/threonine protein kinase Akt (protein kinase B or PKB) is inhibited, which may result in inhibition of the PI3K/Akt signaling pathway, inhibition of tumor cell proliferation, and the induction of tumor cell apoptosis. In addition, this agent appears to induce the activity of protein kinase R-like endoplasmic reticulum kinase (PERK), which plays a key role in the endoplasmic reticulum stress pathway. Activation and dysregulation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. |
| Molecular Formula |
C26H19F3N4O
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|---|---|
| Molecular Weight |
460.4505
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| Exact Mass |
460.151
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| Elemental Analysis |
C, 67.82; H, 4.16; F, 12.38; N, 12.17; O, 3.47
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| CAS # |
742112-33-0
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| Related CAS # |
742112-33-0;1471979-81-3 (HCl);
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| PubChem CID |
10027278
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
683.0±55.0 °C at 760 mmHg
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| Melting Point |
177-180 °C
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| Flash Point |
366.9±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.649
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| LogP |
5.38
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
34
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| Complexity |
711
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C([H])=C(C2C([H])=C([H])C3C4=C([H])C([H])=C([H])C([H])=C4C([H])=C([H])C=3C=2[H])N(C2C([H])=C([H])C(=C([H])C=2[H])N([H])C(C([H])([H])N([H])[H])=O)N=1)(F)F
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| InChi Key |
YULUCECVQOCQFQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/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)
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| Chemical Name |
2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-phenyl} acetamide
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| Synonyms |
AR12; AR 12; AR-12; OSU-03012; OSU03012; OSU 03012
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~11 mg/mL (~23.9 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (5.43 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% methylcellulose+0.2% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1718 mL | 10.8589 mL | 21.7179 mL | |
| 5 mM | 0.4344 mL | 2.1718 mL | 4.3436 mL | |
| 10 mM | 0.2172 mL | 1.0859 mL | 2.1718 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00978523 | Completed | Drug: AR-12 | Solid Tumors Lymphoma |
Arno Therapeutics | August 2009 | Phase 1 |
| NCT01171508 | Completed | Other: Sleep-diary | Anxiety Breast Cancer |
Melissa Voigt Hansen | February 2011 |
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