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PHT-427

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Chemical Structure| 1191951-57-1 同义名 : Akt Inhibitor XIV;CS-0223
CAS号 : 1191951-57-1
货号 : A160471
分子式 : C20H31N3O2S2
纯度 : 99%+
分子量 : 409.609
MDL号 : MFCD18384970
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(61.03 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+95% Corn oil 5 mg/mL

生物活性
靶点

  • Akt

    Akt, Ki:2.7 μM

  • PDK1

    PDK1, Ki:5.2 μM
描述 Phosphatidylinositol 3-kinase (PIK3)/PtdIns dependent protein kinase-1(PDPK1)/Akt signaling plays a critical role in activating proliferation and survival pathways within cancer cells. PHT-427 is a compound designed to bind to the pleckstrin homology (PH) binding domain of signaling molecules. PHT-427 itself (C-12 chain) bound with the highest affinity to the PH domains of both PDPK1 and Akt. PHT-427 inhibited Akt and PDKP1 signaling and their downstream targets in sensitive but not resistant cells and tumor xenografts. The Ki values of PHT-427 are 2.7 and 5.2 µM towards Akt and PDPK1 respectively. RPPA studies in PC-3 prostate cancer cells showed that PHT-427 caused a reduction in phospho-Thr308-Akt, and also in phospho-Ser241-PDPK1 and its downstream targets, phospho-Ser657-PKC and total SGK1. In vivo studies in mice with BxPC-3 and MiaPaCa-2 xenografts treated with a 200 mg/kg dose of PHT-427 showed a decrease in phospho-Ser473-AKT, phospho-Thr308-Akt, phospho-Ser241-PDPK1 and in the PDKP1-specific downstream target phospho-Ser221-RSK[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.21mL

2.44mL

1.22mL

24.41mL

4.88mL

2.44mL
参考文献

[1]Meuillet EJ, Zuohe S, et al. Molecular pharmacology and antitumor activity of PHT-427 a novel AKT/PDPK1 pleckstrin homology domain inhibitor. Mol Cancer Ther, 2010, 9(3), 706-717.

[2]Moses SA, Ali MA, 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.

[3]Madhunapantula SV, Mosca PJ, et al. The Akt signaling pathway: an emerging therapeutic target in malignant melanoma. Cancer Biol Ther. 2011 Dec 15;12(12):1032-49.

[4]Lucero-Acuña A, Jeffery JJ, et al. Nanoparticle delivery of an AKT/PDK1 inhibitor improves the therapeutic effect in pancreatic cancer. Int J Nanomedicine. 2014 Dec 3;9:5653-65.

[5]Meuillet EJ, Zuohe S, Lemos R, Ihle N, Kingston J, Watkins R, Moses SA, Zhang S, Du-Cuny L, Herbst R, Jacoby JJ, Zhou LL, Ahad AM, Mash EA, Kirkpatrick DL, Powis G. 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. doi: 10.1158/1535-7163.MCT-09-0985. Epub 2010 Mar 2. PMID: 20197390; PMCID: PMC2837366.