cyclopamine tartrate

Cyclopamine tartrate (CycT) is a small molecule salt of the steroidal alkaloid cyclopamine, currently under investigation for its potential as an antineoplastic and immunomodulatory agent. While cyclopamine is traditionally recognized as a Smoothened (Smo) inhibitor within the Hedgehog signaling pathway, research conducted at UT Southwestern Medical Center has characterized cyclopamine tartrate as a heme-targeting molecule. It functions by sequestering heme and inhibiting mitochondrial oxidative phosphorylation (OXPHOS), thereby suppressing tumor oxidative metabolism. This metabolic shift reduces tumor hypoxia and alleviates the immunosuppressive nature of the tumor microenvironment. Preclinical studies in triple-negative breast cancer (TNBC) and lung cancer models have demonstrated that CycT treatment leads to significant tumor growth inhibition, increased infiltration of CD8+ T-cells, and enhanced T-cell activation, suggesting its potential utility in combination with immune checkpoint inhibitors.