Tyrosine phosphorylation is a key mechanism for signal transduction and the regulation of a broad set of physiological processes characteristic of multicellular organisms. Hematopoietic protein tyrosine phosphate (HePTP) is a tyrosine phosphatase expressed in hematopoietic cells with specificity for the dephosphorylation of Erk and p38 MAP kinases (MAPKs). It has been found that HePTP is often dysregulated in the preleukemic disorder myelodysplastic syndrome, as well as in acute myelogeneous leukemia. The identified probe ML120 (CID-4302116) selectively inhibits HePTP activity. Since this probe scaffold was discovered through its activity in the HePTP assays with small molecule substrates, it is proposed that this inhibition occurs through direct targeting of the HePTP active site. No time-dependent inhibition is observed as demonstrated by the linear progress curves of the HePTP phosphatase reaction in the presence of various concentrations of the ML120. Thus, small molecule inhibitors of HePTP would be useful as molecular probes for studying the mechanism of signal transduction and MAP kinase regulation. In addition, these probes may have therapeutic potential for the treatment of hematopoietic malignancies, such as acute myeloid leukemia, where HePTP has been reported to be overexpressed.