PHA767491

PHA-767491 is a small-molecule inhibitor that targets the Cdc25 family of dual-specificity phosphatases. In biochemical assays and cell-based studies, it has been described as a potent inhibitor of Cdc25A and Cdc25B, with activity on Cdc25C that varies by assay conditions. By inhibiting Cdc25 phosphatases, PHA-767491 prevents the dephosphorylation and activation of cyclin-dependent kinases (CDKs), notably CDK1 (also known as CDC2). As a result, cells treated with the compound accumulate in G2 phase due to the maintenance of inhibitory phosphorylation on CDKs, leading to reduced cell proliferation in many cancer cell lines.

Pharmacological use and research applications

PHA-767491 is used as a research tool to probe cell-cycle control and checkpoint signaling, particularly the regulation of mitotic entry. It has been employed to study the consequences of Cdc25 inhibition in various cancer models and to explore interactions between DNA damage responses and cell-cycle progression. The compound’s apparent potency is generally characterized as low to mid micromolar in cellular contexts, and its selectivity can depend on concentration and cellular environment. Off-target effects on other phosphatases or kinases may occur at higher concentrations.

Limitations and context

In vivo pharmacokinetic properties and metabolic stability are not well established, and most findings derive from in vitro experiments or early-stage studies. As with many tool compounds, results can be context-dependent, and interpretation should consider potential non-Cdc25 targets at higher doses. PHA-767491 remains primarily a research tool for dissecting Cdc25 function and its role in mitotic regulation and cancer cell biology.