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 |
Akt (Ki = 2.7 μM); PDPK1 (Ki= 5.2 μM); PDK3 (IC50= 313 nM)
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ln Vitro |
PH-427 is a pleckstrin homology domain inhibitor to Akt/PDPK1. PHT-427 can inhibit both Akt and PDPK1 because it significantly lowers phospho-Ser241-PDPK1 and phospho-Thr308-Akt in PC-3 prostate cancer cells at 10 μM. Additionally, PHT-427 prevents the PH domains of Akt and PDPK1 from moving through the plasma membrane. [1] In BxPC-3 cells, PHT-427 induces apoptosis and inhibits AKT phosphorylation with an IC50 of 8.6 μM, primarily on its Ser473 residue and less strongly on its Thr308 residue, without changing the expression of the entire Akt protein. With an IC50 of 65 M, PHT-427 also exhibits antiproliferation in Panc-1 cells.[2]
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ln Vivo |
PHT-427 shows great antitumor activity in BxPC-3 pancreatic, MCF-7 breast and A-549 NSCL cancer xenografts. At doses of 125 to 250 mg/kg, PHT-427 inhibits the growth of tumors in BxPC-3 by up to 80%.[1]
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Enzyme Assay |
All interaction analyses are performed with a Biacore 2000, Biacore 2000 Control Software v3.2, and BIAevaluation v4.1 The Amine Coupling Kit from Biacore is used to immobilize the PH domain GST-fusion proteins (Akt1, IRS1, and PDK1) to a level of 10,000 Response Units (RUs) on a CM5 Sensorchip. High flow rates (30 L/min) are used to inject small molecule analytes at concentrations ranging from 0.1 to 10 the predicted KD. All samples and the running buffer have DMSO concentrations of 1% (v/v) or less.
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Cell Assay |
Serum-starved Panc-1 cells in phenol red-free growth medium are grown on glass-bottom 96-well imaging plates for 16 hours after being transfected with GFP-tagged Akt or PDKP1 PH domains. Following a 4-hour period of PI-103 or PHT-427 treatment, they are stimulated with 50 ng/mL IGF-1 for 10 minutes. Images are captured using an IN Cell Analyzer 1000 instrument with a Nikon Plan Fluor ELWD 20X/0.45 objective loaded and a 300msec exposure time before and after IGF-1 treatment[1].
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Animal Protocol |
Mice: PHT-427 is given orally once to female C57Bl/6 mice at a dose of 200 mg/kg. Three mice are taken out at a time, blood is collected into heparinized tubes, plasma is prepared, and the tubes are frozen at -80°C. 0.2 mL of plasma and 0.1 M sodium phosphate buffer, pH 4.0, are combined for the assay, and the mixture is then extracted for 1 hour by inversion with 1 mL of ethyl acetate. After centrifugation 0.8 mL of the organic layer is removed, evaporated under N2 and redissolved in 0.2 mL ethanol and 10 µL injected onto a Waters Quattro Ultima tandem mass spectrometer using a Phenomenex Luna 3.0 µm, 2.0×50 mm C8 analytical column with detection and quantification by multiple reaction monitoring with the mass spectrometer operating in electrospray positive ionization mode.
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References |
Molecular Formula |
C20H31N3O2S2
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Molecular Weight |
409.61
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Exact Mass |
409.18577
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Elemental Analysis |
C, 58.64; H, 7.63; N, 10.26; O, 7.81; S, 15.66
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CAS # |
1191951-57-1
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Appearance |
Solid powder
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SMILES |
CCCCCCCCCCCCC1=CC=C(C=C1)S(=O)(=O)NC2=NN=CS2
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InChi Key |
BYWWNRBKPCPJMG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H31N3O2S2/c1-2-3-4-5-6-7-8-9-10-11-12-18-13-15-19(16-14-18)27(24,25)23-20-22-21-17-26-20/h13-17H,2-12H2,1H3,(H,22,23)
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Chemical Name |
4-dodecyl-N-(1,3,4-thiadiazol-2-yl)benzenesulfonamide
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Synonyms |
PHT427; PHT-427; PHT 427
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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) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.4413 mL | 12.2067 mL | 24.4135 mL | |
5 mM | 0.4883 mL | 2.4413 mL | 4.8827 mL | |
10 mM | 0.2441 mL | 1.2207 mL | 2.4413 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.
Effects of PHT-427 in cells. Cancer Res, 2009, 69(12), 5073-5081. |
Antitumor activity of PHT-427 analogs td> |
In vivo effects of PHT-427 td> |