Indomethacin Derivatives as Potential Anticancer Agents ‐ Daybreak of New Epoch

Abstract Non‐steroidal anti‐inflammatory drugs (NSAIDs) are extensively prescribed pharmaceutical agents worldwide. Due to their analgesic, antipyretic, and anti‐inflammatory properties, they are used in clinical practice for the treatment of numerous inflammatory diseases. The mechanism of action primarily involves the inhibition of prostaglandin synthesis mediated by cyclooxygenases (COX), key enzymes of the inflammatory cascade. Indomethacin, a non‐selective derivative of indole‐3‐acetic acid exhibits diverse mechanisms to exert its anti‐tumor effects, including angiogenesis suppression, induction of apoptosis, and reduction of tumorigenesis through immune modulation. Numerous studies suggest that derivatives of indomethacin may inhibit cell proliferation and reduce levels of anti‐apoptotic proteins through COX‐independent mechanisms. Given the diverse potential mechanisms through which indomethacin impacts cancer progression, this review provides an overview of structural analogs that possess antitumor activity and outlines future directions in developing new candidates that may have substantial efficacy in cancer therapy.