product name BQU57
Description: BQU57, a derivative of RBC8, is a selective GTPase Ral inhibitor relative to the GTPases Ras and RhoA. BQU57 is a derivative of RBC8. It show selectivity for Ral relative to the GTPases Ras and RhoA and inhibit tumour xenograft growth. The binding of BQU57 to RalB–GDP was with a dissociation constant (Kd) of 7.760.6 mM by using isothermal titration calorimetry (ITC). It was similar to the results from surface plasmon resonance (SPR), which had a Kd value of 4.761.5 mM. RBC8 or BQU57 can effectively inhibited the colony formation in soft agar of the Ral-dependent lines H2122 and H358, but not H460 or Calu-6.
References: Nature. 2014 Nov 20;515(7527):443-7.
334.1
Formula
C16H13F3N4O
CAS No.
1637739-82-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 66 mg/mL (197.5 mM)
Water: <1 mg/mL
Ethanol: 20 mg/mL (59.9 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: In both the H2122 and H358 cell lines, BQU57 inhibits both RalA and RalB activation, and thus causes cell growth inhibition. Kinase Assay: This assay used J82 human bladder cancer cells that stably expressed Flag-tagged RalA. The Flag epitope tag greatly increased the sensitivity and dynamic range of the assay compared with using Ral-specific antibodies for detection. Cells were treated with each of the 88 compounds (tested at 50 mM), and then extracts were prepared. The binding of Flag–RalA to recombinant RALBP1 that had been immobilized in 96-well plates was quantified. In this assay, RalA binding reflects Ral’s GTP loading and capacity for effector activation. Cell Assay: Growth inhibition on human lung cancer cells by the compounds are measured under anchorage-independent conditions in soft agar. Cells are seeded into 6-well plates (coated with a base layer made of 2.0 mL of 1% low-melting-point agarose) at 15,000 cells per well in 3.0 mL of 0.4% low-melting-point agarose containing various concentration of drug. Two to four weeks (depending on cell line) after incubation, cells are stained with 1.0 mg/mL Nitro Blue Tetrazolium and colonies are counted under a microscope. The IC50 values are defined as the concentration of drug that resulted in 50% reduction in colony number compared to DMSO treated control. After 48 hr, cells are subjected to the soft agar colony formation assay. |
|---|---|
| In Vivo | In mice bearing human lung H2122 tumors, BQU57 (50 mg/kg, i.p.) significantly inhibits activation of both RalA and RalB, and causes dose-dependent tumor growth inhibition. |
| Animal model | Mice bearing human lung H2122 tumors |
| Formulation & Dosage | Dissolved in DMSO; 50 mg/kg; i.p. injection |
| References | Nature. 2014 Nov 20;515(7527):443-7. |
