9-ING-41 + lomustine

9-ING-41 + lomustine is an investigational combination therapy consisting of 9-ING-41, a potent and selective small molecule inhibitor of glycogen synthase kinase 3 beta (GSK-3β), and lomustine, an alkylating nitrosourea chemotherapeutic agent. **9-ING-41** acts by inhibiting GSK-3β, a serine/threonine kinase implicated in cancer cell growth, survival, chemotherapy resistance, and modulation of oncogenic pathways such as beta-catenin and cyclin D1. Inhibition of GSK-3β by 9-ING-41 leads to cell cycle arrest, autophagy induction, apoptosis in tumor cells[7][10], reversal of chemotherapy resistance[4][8], anti-fibrotic effects[5][9], and stimulation of NK/T-cell effector function[8]. **Lomustine** is a well-established oral alkylating agent that cross-links DNA and RNA to inhibit cancer cell replication. The rationale for combining these agents is that GSK‑3β inhibition may sensitize tumors to cytotoxic chemotherapy like lomustine by overcoming drug resistance mechanisms. This combination is being evaluated in clinical trials for patients with advanced or refractory malignancies.