salinomycin

Salinomycin is a polyether ionophore antibiotic originally isolated from the bacterium *Streptomyces albus*. It is primarily used as an antibacterial and coccidiostat agent in veterinary medicine. Salinomycin exhibits high antimicrobial activity against Gram-positive bacteria, including resistant strains such as methicillin-resistant *Staphylococcus aureus* (MRSA), and is inactive against most Gram-negative bacteria and fungi[4][6]. In recent years, it has gained significant attention for its potent anticancer properties—particularly its ability to selectively target and kill cancer stem cells (CSCs) across various tumor types including breast, prostate, ovarian, lung, and colorectal cancers[3][4][5]. The mechanism of action involves acting as a potassium ionophore that disrupts cellular ion homeostasis by facilitating bidirectional transport of K+ ions across cell membranes[7]. This leads to altered osmotic pressure and cell death in susceptible organisms or cells. In cancer research settings, salinomycin interferes with multiple signaling pathways critical for CSC survival—including Wnt/β-catenin, Hedgehog, Notch, PI3K/Akt/mTOR—and induces apoptosis through mechanisms such as lysosomal iron sequestration (leading to ferroptosis), increased reactive oxygen species production (ROS), DNA damage response activation (e.g., γH2AX phosphorylation), inhibition of anti-apoptotic genes like BCL-2/BCL-XL/BIRC5/survivin expression[3][4][5][8]. Preclinical studies have shown that it can overcome drug resistance in cancer cells more effectively than some standard chemotherapeutics like paclitaxel. Salinomycin remains under investigation for human use in oncology; it is not currently approved for this indication. Developed by Verastem.

Other names

monensin Acoxistacsalinomycine