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Biological Activity:

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BQU57 is a potent and selective GTPase Ral Inhibitor. It showed selectivity for Ral relative to the GTPases Ras and RhoA and inhibited tumour xenograft growth to a similar extent to the depletion of Ral using RNA interference. It inhibited the binding of Ral to its effector RALBP1, as well as inhibiting Ral-mediated cell spreading of murine embryonic fibroblasts and anchorage-independent growth of human cancer cell lines. The binding of the BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasmon resonance and 1H-15N transverse relaxation-optimized spectroscopy (TROSY) NMR spectroscopy. The Ras-like GTPases RalA and RalB are important drivers of tumour growth and metastasis. BQU57 that blocks Ral function would be valuable as research tools and for cancer therapeutics.

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How to Use:

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In vitro: ?BUQ57 was used at 5-15 μM final concentration in various in vitro assays.

In vivo:?BUQ57 was dosed to mice bearing human lung cancer cell line H2122 xenografts by intraperitoneal injection at 50 mg/Kg once per day.?

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Reference:

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1. 1.?1. Yan C, et al. Discovery and characterization of small molecules that target the GTPase Ral. (2014) Nature. 515(7527):443-7.