HAMNO

HAMNO (CAS No.: 138736-73-9) is a selective small-molecule inhibitor of replication protein A (RPA), a key single-stranded DNA-binding complex that regulates DNA replication, repair, and the cellular response to replication stress, and is widely studied in oncology and DNA damage response research. Mechanistically, HAMNO targets the DNA binding domain F (DBD-F) of the RPA70 subunit, disrupting protein–DNA interactions and impairing downstream signaling, including inhibition of ATR kinase autophosphorylation and suppression of ATR-mediated phosphorylation of RPA32 at Ser33, thereby amplifying replication stress and DNA damage signaling. In cancer cell models, particularly head and neck squamous cell carcinoma lines, HAMNO induces dose-dependent increases in γ-H2AX staining indicative of DNA double-strand breaks, with pronounced effects during S phase, and reduces clonogenic survival; these effects are further enhanced when combined with DNA-damaging agents such as etoposide, demonstrating synergistic suppression of tumor cell proliferation. In vivo, HAMNO has been shown to inhibit tumor growth in xenograft models, especially in combination regimens, supporting its utility as a chemical probe for studying replication stress pathways and as a potential lead compound in anticancer drug discovery. Experimental applications typically employ low to moderate micromolar concentrations in vitro and dose regimens in animal studies that vary depending on study design and therapeutic combination strategies.