Technology

The Apogee of Therapeutic Innovation

Sphingosine kinase (SK) is an innovative molecular target for therapy because of its critical role in sphingolipid metabolism, which is known to regulate cell proliferation and activation.  SK produces sphingosine-1-phosphate which promotes mitogenesis and concurrently depletes ceramide, thereby inhibiting apoptosis.  SK can act as an oncogene, and is frequently overexpressed in a variety of human tumors.

SK is also a critical mediator of the actions of inflammatory cytokines, such as TNFα, and angiogenic growth factors, such as VEGF.  Furthermore, serum levels of sphingosine-1-phosphate are highly correlated with the incidence of cardiovascular disease.  Therefore, inhibitors of SK are expected to have utility for the treatment of a variety of hyperproliferative, cardiovascular, inflammatory and angiogenic diseases.

Apogee Biotechnology Corporation novel sphingosine kinase inhibitors:   (Lead compound, ABC294640)

  • are the only “drug-like” SK inhibitors reported to date;
  • do not inhibit a broad range of protein kinases;
  • block signaling pathways required for VEGF- and TNFα-mediated cell activation;
  • are orally bioavailable and have excellent pharmacokinetics;
  • are non-toxic to mice and rats;
  • inhibit syngeneic and xenografted tumor growth in vivo;
  • inhibit VEGF-induced vascular leakage in vivo;
  • inhibit diabetes-induced retinal vascular leakage in vivo;
  • inhibit collagen- and adjuvant-induced arthritis in vivo;
  • inhibit DSS- and TNBS-induced inflammatory bowel disease in vivo;
  • inhibit experimental lupus in vivo;
  • inhibit liver ischemia-reperfusion injury in vivo; and
  • inhibit kidney ischemia-reperfusion injury in vivo.

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