OSU-03012 is a potential first-in-class, orally available PDK-1 inhibitor that targets the Akt pathway, and also possesses activity in alternate pathways to target apoptosis and angiogenesis. Preclinical data have demonstrated activity in multiple tumor types and synergistic activity with other agents including Avastin®, Herceptin®, Tarceva®, Gleevec® and tamoxifen. Arno plans to initiate Phase I studies of OSU-03012 in 2009.




Publications

• Sensitizing estrogen-receptor – negative breast cancer cells to tamoxifen with OSU-03012, a novel celecoxib-derived phosphoinositide-dependent protein kinase – 1 /Akt signaling inhibitor. Shu-Chuan Weng, Yoko Kashida, Samuel K. Kulp et al. Mol Cancer Ther 2008; 7(4):800-8
  
• Targeting Endoplasmic Reticulum Stress and Akt with OSU-03012 and Gefitinib or Erlotinib to Overcome Resistance to Epidermal Growth Factor Receptor Inhibitors -- Wang et al. 68 (8): 2820 -- Cancer Research
  http://cancerres.aacrjournals.org/cgi/content/abstract/68/8/2820?etoc
• Cen L, Hsieh FC, Lin HJ, Chen CS, Qualman SJ and Lin J, PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. British Journal of Cancer (2007).
• Sargeant AM, Klein RD, Rengel RC et al., Chemopreventive and Bioenergetic Signaling Effects of PDK1/Akt Pathway Inhibition in a Transgenic Mouse Model of Prostate Cancer. Toxicologic Pathology, 35:549-561, 2007.
• Yacoub A, Park MA, Hanna D et al., OSU-03012 Promotes Caspase-Independent but PERK-, Cathepsin B-, BID-, and AIF-Dependent Killing of Transformed Cells. Molecular Pharmacology 70:589-603, 2006.
• McCubrey JA, LaHair MM, and Franklin RA, OSU-03012 in the Treatment of Glioblastoma. Molecular Pharmacology 70:437-439, 2006.
• Tseng PH, Lin HP, Zhu J et al., Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance. Blood, 15 May 2005 - Volume 105 - Number 10.
• Zhu J, Huang JW, Tseng PH et al., From the Cyclooxygenase-2 Inhibitor Celecoxib to a Novel Class of 3-Phosphoinositide-Dependent Protein Kinase-1 Inhibitors. Cancer Research 64, 4309-4318, June 15, 2004.