Dxr2-017

Dxr2-017 is a novel small molecule therapeutic candidate discovered through a physics-based protein structure analysis platform that identifies unique, non-functional surface motifs on proteins. Developed by researchers at the University of Nebraska Medical Center (UNMC), Northwestern University, and the University of Chicago, the compound was identified by screening a 60 million compound library against unique protein clefts. Dxr2-017 specifically targets a structural motif on the bacterial protein 1-deoxy-D-xylulose 5-phosphate reductoisomerase (Dxr2); however, it exploits evolutionarily conserved 3D structural features to induce anoikis—a form of programmed cell death triggered by cell detachment—in human cancer cells. Preclinical studies have demonstrated that Dxr2-017 possesses potent anti-tumor activity, particularly against melanoma, with an IC50 in the low nanomolar range (12-19 nM), as well as efficacy against colon and breast cancer. Notably, the compound exhibits a high therapeutic index, with minimal inhibitory effects on human bone marrow stem cells at concentrations over 2100-fold higher than its effective dose.