9-ING-41 + irinotecan + temozolomide

**9-ING-41 + irinotecan + temozolomide** is an investigational combination therapy comprising 9-ING-41, a first-in-class, intravenously administered, maleimide-based small molecule that is a potent and selective inhibitor of Glycogen Synthase Kinase-3 beta (GSK-3β), combined with the cytotoxic chemotherapeutics irinotecan (a topoisomerase I inhibitor) and temozolomide (an alkylating agent)[1][3]. **9-ING-41** exerts anti-tumor effects by downregulating NF-κB and decreasing expression of its target genes (such as cyclin D1, Bcl-2, XIAP, and Bcl-XL), leading to cell cycle arrest and increased apoptosis, particularly effective against chemotherapy-resistant cancers[2][3]. **Irinotecan** inhibits topoisomerase I, causing DNA damage and cell death, and **temozolomide** methylates DNA to induce apoptosis and cytotoxicity. The rationale behind this combination is to overcome resistance in advanced cancers—especially gliomas and other refractory malignancies—through synergistic blockade of survival pathways and induction of apoptosis. Clinical trials (e.g., Actuate 1801) are evaluating its safety, tolerability, and efficacy in patients with advanced solid tumors and gliomas[1][2][3]. No unique trade or brand name exists for this exact combination; it is primarily referenced by its constituents in trial documentation.