GABA(A)-compound 1b

GABA(A)-compound 1b is a novel small molecule antagonist of the γ-aminobutyric acid type A receptor (GABAAR) currently under investigation for the treatment of high-grade gliomas (HGG). Identified through network analysis of patient-derived transcriptomic data, the compound targets GABAAR subunits—including α1, γ2, and α5—that are significantly upregulated at the invasive leading edge of tumors such as glioblastoma and pediatric diffuse midline glioma. By antagonizing these receptors, GABA(A)-compound 1b disrupts the neuronal-like signaling pathways that facilitate tumor cell proliferation and invasion into healthy brain tissue. Preclinical studies in glioblastoma organoids (GBOs) have shown that the compound effectively suppresses tumor growth and enhances the therapeutic effects of standard-of-care radiation and temozolomide. The compound is being developed in collaboration with the drug discovery company Combinatics.