BQU57

**BQU57** is a small molecule inhibitor of the Ras-like GTPases **RalA** and **RalB**, binding selectively to their GDP-bound forms with a Kd of 7.7 µM for RalB (determined by ITC). It inhibits Ral activation (by >90% at 10 µM in 3 h), anchorage-independent colony formation in Ral-dependent lung cancer cell lines H2122 (IC50 2.0 µM) and H358 (IC50 1.3 µM) in soft agar assays, and xenograft tumor growth in mice (70% suppression with 50 mg/kg daily i.p. dosing), with favorable pharmacokinetics (plasma T1/2 1.5 h, AUC0-5h 28.6 µg·h/mL post 50 mg/kg i.p.). Developed via structure-based discovery from a virtual screen at the University of Colorado Cancer Center, it shows selectivity over Ras and Rho GTPases and has been explored in preclinical models of lung cancer, triple-negative breast cancer, and intervertebral disc degeneration via NF-κB pathway inhibition.[1][4][7][9][14][15]