生物活性

• 靶点

  Akt3 IC50:2.12μM

  Akt2 IC50:210nM

  Akt1 IC50:58nM

• 描述Akt/PKB (protein kinase B) is a serine/threonine kinase which has a key role in the regulation of survival and proliferation. There are three isoforms of human Akt (Akt1, Akt2 and Akt3) and they all have an N-terminal PH (pleckstrin homology) domain and a kinase domain separated by a 39-amino-acid hinge region^[3]. AKT inhibitor VIII（Akti-1/2), a cell-permeable quinoxaline compound, is an non-ATP-competitive inhibitor with IC50s of 58 nM, 210 nM, and 2119 nM towards Akt1, Akt2, and Akt3, respectively^[4]. This inhibitor prevents phosphorylation of PKB isoforms(Akt1, Akt2 and Akt3), possibly by interfering with the PH domain and/or hinge region of PKB. In vivo study, it was showed that Akti-1/2 can completely inhibit thrombin-mediated phosphorylation of PKB and its downstream substrate GSK3β at a concentration of 5 μM^[5]. Akti-1/2 treatment induced an increase in NOXA protein levels and a down-regulation of the levels of MCL-1, a critical survival protein in chronic lymphocytic leukemia (CLL) cells, which indicated that Akti-1/2 might be a new therapeutic option for the treatment of CLL^[6].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  184B5 cells	20 μM	Cytotoxicity assay	-	Cytotoxicity against human 184B5 cells at 20 uM chloroquine by SRB assay, GI50=25.76 μM	18691894
  22RV1 cell	-	Growth inhibition assay	-	Inhibition of human 22RV1 cell growth in a cell viability assay, IC50=6.61424 μM	SANGER
  23132-87 cell	-	Growth inhibition assay	-	Inhibition of human 23132-87 cell growth in a cell viability assay, IC50=0.75938 μM	SANGER

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01257594	Brain Cancer	Not Applicable	Unknown	December 2016	United States, New Jersey ... more >> Memorial Sloan-Kettering at Basking Ridge Basking Ridge, New Jersey, United States, 07920 United States, New York Memorial Sloan-Kettering Cancer Center at Commack Commack, New York, United States, 11725 Columbia University Medical Center New York, New York, United States, 10032 Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 Collapse <<
  NCT00897663	-	-	Completed	-	United States, Arizona ... more >> Mayo Clinic Scottsdale Scottsdale, Arizona, United States, 85259-5499 United States, Florida Mayo Clinic - Jacksonville Jacksonville, Florida, United States, 32224 United States, Iowa Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa, United States, 51101 Mercy Medical Center - Sioux City Sioux City, Iowa, United States, 51102 St. Luke's Regional Medical Center Sioux City, Iowa, United States, 51104 United States, Minnesota Mayo Clinic Cancer Center Rochester, Minnesota, United States, 55905 United States, North Dakota Medcenter One Hospital Cancer Care Center Bismarck, North Dakota, United States, 58501 Mid Dakota Clinic, PC Bismarck, North Dakota, United States, 58501 St. Alexius Medical Center Cancer Center Bismarck, North Dakota, United States, 58502 United States, South Dakota Rapid City Regional Hospital Rapid City, South Dakota, United States, 57701 Collapse <<

• 参考文献

• [1] Logie L, Ruiz-Alcaraz AJ, et al. Characterization of a protein kinase B inhibitor in vitro and in insulin-treated liver cells. Diabetes. 2007 Sep;56(9):2218-27.

  [2] Lindsley CW, Zhao Z, et al. Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):761-4.

  [3] Barnett SF, Defeo-Jones D, Fu S, Hancock PJ, Haskell KM, Jones RE, Kahana JA, Kral AM, Leander K, Lee LL, Malinowski J, McAvoy EM, Nahas DD, Robinson RG, Huber HE. Identification and characterization of pleckstrin-homology-domain-dependent and isoenzyme-specific Akt inhibitors. Biochem J. 2005 Jan 15;385(Pt 2):399-408. doi: 10.1042/BJ20041140. PMID: 15456405; PMCID: PMC1134710.

  [4] Lindsley CW, Zhao Z, Leister WH, Robinson RG, Barnett SF, Defeo-Jones D, Jones RE, Hartman GD, Huff JR, Huber HE, Duggan ME. Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):761-4. doi: 10.1016/j.bmcl.2004.11.011. PMID: 15664853.

  [5] Hunter RW, Harper MT, Hers I. The PKB inhibitor Akti-1/2 potentiates PAR-1-mediated platelet function independently of its ability to block PKB. J Thromb Haemost. 2008 Nov;6(11):1923-32. doi: 10.1111/j.1538-7836.2008.03140.x. Epub 2008 Aug 28. PMID: 18761726.

  [6] de Frias M, Iglesias-Serret D, Cosialls AM, Coll-Mulet L, Santidrián AF, González-Gironès DM, de la Banda E, Pons G, Gil J. Akt inhibitors induce apoptosis in chronic lymphocytic leukemia cells. Haematologica. 2009 Dec;94(12):1698-707. doi: 10.3324/haematol.2008.004028. Epub 2009 Oct 8. PMID: 19815839; PMCID: PMC2791940.

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