CP-EPS8-NLS is a peptide derived from the nuclear localization signal (NLS) of epidermal growth factor receptor (EGFR) pathway substrate no.8 (EPS8) (amino acids 298-310), conjugated at the N-terminal to Tat (48 - 60) to facilitate cell penetration. EPS8 is an important signaling molecule that integrates multiple pathways, and elevated EPS8 expression levels are critical in tumourigenesis, proliferation, invasion and metastasis. NLS residues of tumour associated proteins are crucial for cell cycle progression and the core NLS (298-310) domain acts to guide EPS8 to the nucleus. CP-EPS8-NLS interferes with the nuclear translocation of EPS8, downregulating EPS8 expression and blocking its downstream pathways. In a nude mouse xenograft assay, CP-EPS8-NLS potently lowers acute myeloid leukemia (AML) tumour sizes, an effect synergistic with the chemotherapeutic agents daunorubicin, cytarabine and adriamycin.
