E7/PTPN14 inhibitor compound 20 (F0470-0212) is a first-in-class inhibitor of PPI of HPV E7 oncoprotein and the cellular phosphatase PTPN14 (E7/PTPN14 interaction) with IC50 of 4.7 uM in ELISA-based assays, selectively affects the viability of HPV-positive cervical cancer cells.
E7/PTPN14 inhibitor compound 20 remarkably affects the viability of both HPV-positive cancer cell lines with IC50 of 15.2 uM in HeLa cells and 6.6 uM in CaSki cells, without showing toxicity (IC50 > 250 μM) against either HPV-negative C33A cancer cells or non-tumoral cells.
E7/PTPN14 inhibitor compound 20 (25 uM) increases PTPN14 levels and induces the cytoplasmic relocalization and transcriptional inactivation of YAP in HPV18-positive HeLa cells.
E7/PTPN14 inhibitor compound 20 affects the proliferation, clonogenicity, migration/invasion capacity, and stem-cell survival of HPV-positive cancer cells.
E7/PTPN14 inhibitor compound 20 is active against different high-risk HPV genotypes, thus exhibiting a potential broad-spectrum activity.