NSC 370284 is a small molecule that directly binds to and inhibits STAT3/5, significantly and selectively suppresses the viability of AML cells with high level of TET1 expression both in vitro and in vivo.

NSC-370284 exhibited the most significant effects in inhibiting cell viability of all four TET1-high AML cell lines, whereas showing no significant inhibition on viability of NB4/t(15;17) AML cells [1].The direct binding of STAT3 and STAT5 on the TET1 loci was further validated in MONOMAC-6 cells, and such binding could be disturbed by NSC-370284 treatmen [1].Analysis suggested a potential direct binding of NSC-370284 to the conserved DNA-binding domain (DBD) of STAT3 or STAT5 [1].

NSC 370284 treatments significantly inhibited MLL-AF9-induced AML in secondary bone marrow transplantation (BMT) recipient mice, and 57% (4 out of 7) of the NSC-370284-treated mice were cured, as the pathological morphologies in peripheral blood (PB), BM, spleen, and liver tissues all turned to normal. [1]