KA44

KA44 is a novel hybrid homo-aza (lactam) steroidal antimetabolite being investigated for the treatment of gastrointestinal malignancies, specifically pancreatic and colorectal cancers. It belongs to a class of steroidal conjugates designed to enhance selectivity and toxicokinetics compared to conventional antimetabolites like 5-fluorouracil and methotrexate. KA44 acts as a dual inhibitor of thymidylate synthase (TS) and dihydrofolate reductase (DHFR), leading to the inhibition of DNA synthesis, induction of apoptosis, and cell cycle arrest. Preclinical studies have demonstrated its cytostatic efficacy against various carcinoma cell lines, providing a rationale for its further evaluation as a next-generation therapeutic for resistant gastrointestinal cancers.