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hexyl cuban-1-yl biguanide
- Development stage
- Preclinical
- Lead developer
- Mayo Clinic
- Modality
- Small Molecules
- Administration
- Intraperitoneal
01
Overview
Hexyl cuban-1-yl biguanide (HCB) is a preclinical small molecule biguanide derivative developed by the University of Minnesota and Mayo Clinic. It acts as a potent inhibitor of Cytochrome P450 3A4 (CYP3A4) arachidonic acid (AA) epoxygenase activity, thereby blocking the biosynthesis of immunosuppressive and tumor-promoting epoxyeicosatrienoic acids (EETs). By inhibiting EET biosynthesis, HCB suppresses mitochondrial oxidative phosphorylation (OXPHOS) and reverses tumor hypoxia. Additionally, HCB has been shown to suppress the N-glycosylation of immune checkpoint proteins B7-H3 and B7-H4, leading to decreased intratumoral regulatory T cells (Tregs) and increased CD8+ T cells. It is being investigated for the treatment of hormone therapy-resistant (HTR) and multiply resistant (MR) ER+/HER2- breast cancers, particularly in combination with standard-of-care agents like fulvestrant and palbociclib.
- Other names
- HCBhexyl-(cuban-1-yl-methyl)-biguanidehexyl-cuban-1-yl biguanidehexyl-cuban1-yl biguanidehexyl-cuban 1-yl biguanide
02
Targets
VTCN1 (V-set domain containing T cell activation inhibitor 1)CYP3A4 (Cytochrome P450 3A4)B7-H3
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