RGN6024 is an orally active, reversible small molecule that can penetrate the blood-brain barrier and acts as a microtubule (tubulin) destabilizer. It inhibits microtubule polymerization in both biochemical and cellular assays. RGN6024 binds to the colchicine-binding site of β-tubulin with affinity constants of Kd= 6.7 μM (SPR) and Kd= 7.4 μM (tryptophan assay), inducing G2/M phase arrest in glioblastoma (GB) cells. The compound remains effective in cells overexpressing βIII-tubulin. Additionally, RGN6024 is able to suppress tumor growth in glioblastoma (GB) xenograft mouse models. This compound is applicable for research in glioblastoma (GB).

RGN6024, when applied at a concentration of 100 nM for 48 hours, binds to the colchicine binding site of β-tubulin and disrupts microtubule morphology in U87 glioblastoma cells. With treatment extending to 72 hours, RGN6024 reversibly decreases the viability of glioblastoma cells, exhibiting an IC50 of 85 nM in U87 cells, 23 nM in LN-18 cells, and 120 nM in BT142 cells. In a cell viability recovery assay involving U87 cells, RGN6024 (0.001-100 μM, 6 hours) demonstrates high reversibility, with a post-dilution IC50 of 2482 nM, a 30-fold shift from the initial 81.6 nM. Additionally, at 250 nM for 48 hours, RGN6024 induces G2/M phase arrest in U87 cells and is relatively unaffected by βIII-tubulin overexpression in HeLa cells.

RGN6024, administered orally at doses of 7.5-25 mg/kg either daily or for 5 days followed by a 2-day break over a 15-day period, has been shown to inhibit tumor growth in a Temozolomide (TMZ)-resistant glioblastoma xenograft mouse model. Additionally, administering RGN6024 at 15-20 mg/kg orally, once or twice daily, or every other day for 49 days, is effective in reducing tumor growth and extending survival in an orthotopic glioblastoma xenograft mouse model.