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  • PHT-427
PHT-427的可视化放大

PHT-427

An inhibitor of Akt and PDPK1

原价
¥412-2975
价格
330-2380
PHT-427的二维码

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  • 货号: ajci8430
  • CAS: 1191951-57-1
  • 别名: 4-十二烷基-N-1,3,4-噻二唑-2-基苯磺酰胺
  • 分子式: C20H31N3O2S2
  • 分子量: 409.61
  • 纯度: >98%
  • 溶解度: ≥ 20.5mg/mL in DMSO, ≥ 51.1 mg/mL in EtOH with ultrasonic
  • 储存: Store at -20°C
  • 库存: 现货

Background

PHT-427 is an inhibitor of Akt and PDPK1 (Ki =2.7 μM and 5.2 μM, respectively).


Akt is a serine/threonine-specific protein kinase that plays a vital role in multiple cellular processes including glucose metabolism, apoptosis, cell proliferation, transcription and cell migration etc.


In BxPC-3 cells, PHT-427 showed inhibition upon Akt function with IC50 value of 8.6±0.8 μM and for its downstream substrates. PHT-427 reduced the Akt phosphorylation on Ser473 residue and did not decrease total Akt protein level. PHT-427 also inhibited p70S6K and GSK3β in a dose-dependent manner. [1][2]


In SCID (severe combined immunodeficiency) mice of BxPC-3 pancreatic cancer xenografts, administration of PHT-427 exerted prominent antitumor activity that halted tumor growth. PHT-427 in combination with erlotinib exhibited greater than additive antitumor activity in NSC lung cancer and with paclitaxel in breast cancer. [1][2]

参考文献:
1. Meuillet EJ, Zuohe S, Lemos R et al.? Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17.
2. Moses SA, Ali MA, Zuohe S et al.? In vitro and in vivo activity of novel small-molecule inhibitors targeting the pleckstrin homology domain of protein kinase B/AKT. Cancer Res. 2009 Jun 15;69(12):5073-81.

Protocol

Cell experiment:

Panc-1 cells stably transfected with green fluorescent protein (GFP) tagged Akt or PDKP1 PH domains are serum starved in phenol red free growth medium on glass-bottom 96-well imaging plates for 16 hours. They are then treated with PHT-427 at 1, 5, and 10 μM or PI-103 for 4 hr, and stimulated with 50 ng/mL IGF-1 for 10 min. Images are taken before and after IGF-1 treatment using an IN Cell Analyzer 1000 instrument with a Nikon Plan Fluor ELWD 20X/0.45 objective loaded and using a 300msec exposure time[1].

Animal experiment:

Mice[1] Female C57Bl/6 mice are administered PHT-427 as a single oral dose of 200 mg/kg. The mice are killed at different times (3 mice at each time point), blood collected into heparinized tubes and plasma prepared and stored frozen at -80°C. For assay 0.2 mL plasma is mixed with 0.2 mL of 0.1 M sodium phosphate buffer, pH 4.0, and extracted for 1 hr by inversion with 1 ml 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.

参考文献:

[1]. Meuillet EJ, et al. Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 pleckstrin homology domain inhibitor. Mol Cancer Ther. 2010 Mar;9(3):706-17.

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