Stemline - Model XPO1 - Regulate Nuclear Export
XPO1 has been shown to regulate nuclear export of many of the major tumor suppressor proteins and oncogenic cell growth regulators. Overexpression of XPO1 has been reported in many cancer types and is associated with aggressive tumor behavior and poor patient prognosis. Inhibition of XPO1 has been shown to restore tumor suppressor function and proper cell cycle regulation, leading to apoptosis of cancer cells. XPO1 has also been shown to be a clinically validated target in both solid and hematological cancers. SL-801 has demonstrated broad and SL-801 has demonstrated broad and potent preclinical activity in a wide array of solid and hematologic tumors, as well as neurologic disorders, in both in vitro and in vivo xenograft experiments.
Details
In a screening against 240 cancer cell lines, SL-801 possessed strong anti-tumor activity, with 50% growth inhibitory values less than 10 nM in 21.3% of cell lines and less than 100 nM in 95.8% of cell lines. As a single agent, SL-801 also significantly prolonged overall survival and inhibited tumor growth in several mouse xenograft models of human multiple myeloma, as well as in xenograft models of acute lymphoblastic leukemia, non-small cell lung cancer, and prostate carcinoma, in well-tolerated single-dose or multidose regimens. SL-801’s ability to reversibly bind XPO1 may offer the potential to improve the therapeutic index in humans
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