9-ING-41 + doxorubicin

**9-ING-41 + doxorubicin** is an investigational combination therapy comprising 9-ING-41, a first-in-class, intravenously administered, maleimide-based small molecule, and doxorubicin, an anthracycline chemotherapeutic. 9-ING-41 is a potent and selective inhibitor of the serine/threonine kinase glycogen synthase kinase-3 beta (GSK-3β), a target involved in tumor progression and chemotherapy resistance through modulation of oncogenes (such as c-Myc, beta-catenin, cyclin D1), cell cycle regulators, and anti-apoptotic proteins. The inhibition of GSK-3β by 9-ING-41 downregulates the NF-κB pathway, decreases expression of NF-κB-regulated anti-apoptotic genes (including Bcl-2, XIAP, Bcl-XL, cyclin D1), and restores sensitivity of cancer cells to cytotoxic therapy. This combination is being evaluated in advanced refractory malignancies for its potential to enhance antitumor efficacy versus standard therapy alone[1][3]. Doxorubicin acts via DNA intercalation and inhibition of topoisomerase II, leading to DNA damage and apoptosis; it is standard in treatment of several solid tumors and hematological malignancies.