HAMNO (NSC111847)

Description: HAMNO (formerly known as NSC-111847) is a novel, potent and selective protein interaction inhibitor of replication protein A (RPA). RPA is thought to interact with proteins involved in the replication stress response. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions that rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Therefore, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress.

References: Cancer Res. 2014 Sep 15; 74(18):5165-72.