Using single-nucleus RNA sequencing from glioblastoma (GBM) patient tissues, we identified the homeobox (HOX) superfamily as a GBM-specific cellular target. HOX superfamily proteins are transcription factors that regulate organ growth during embryonic development. In normal physiology, HOX genes are silenced after development. In GBM, HOX expression are reported as negative prognostic/survival factors. Through structural biological analysis, rational drug design, hit validation, and subsequent in vitro binding assays, we have created a novel compound, YCSL-H10, which experimentally shows ~1.5 nM IC50 in HOXD10-DNA complexes. This compound represents a strong candidate for the development of HOX-targeted imaging and treatment via radioisotopic labelling. With the $300K Blavatnik Award, the plan includes cell culture assays with human GBM samples, YCSL-H10 radiolabeling, in vivo imaging on rodent and NHP models, and toxicity testing, leading to regulatory applications.