angubindin-1

Angubindin-1 is a **synthetic peptide** derived from the angulin-1 binding domain of the Clostridium perfringens iota toxin[1]. Its primary action is as a **selective binder to angulin-1/LSR and angulin-3** at **tricellular tight junctions** (tTJs), which are specialized junctions where three epithelial or endothelial cells meet. By binding angulin-1/LSR, angubindin-1 transiently disrupts tricellular tight junction integrity, leading to a reversible decrease in epithelial and endothelial barrier function. This action increases **paracellular permeability**, allowing for enhanced absorption of large molecules and facilitating drug delivery across barriers like the intestinal epithelium and the blood-brain barrier (BBB)[1][2][3][4][5]. Mechanistically, angubindin-1 regulates the epithelial barrier via **the JNK/cofilin/actin cytoskeleton pathway** at tricellular contacts[1]. Preclinically, angubindin-1 has been shown to: - Increase the permeability of the BBB, enabling efficient, transient delivery of antisense oligonucleotides to the central nervous system without overt adverse effects[2][3][5]. - Enhance delivery of chemotherapeutic agents (e.g., Doxil) to brain tumors by enhancing blood-tumor barrier permeability and improving therapeutic efficacy in rat glioma models[4]. - Temporarily increase cell migration through modulation of actin and various signaling pathways. Angubindin-1 is investigated as a **paracellular absorption enhancer** and as a research tool for **drug delivery systems targeting the CNS and cancer**. There are no clinical approvals or commercial products as of the latest evidence.