LY-2784544 is an orally-available, imidazolopyridazine-based inhibitor of the JAK2-V617F mutation, the most common abnormality in Bcr-Abl-negative myeloid proliferative neoplasms. [1] Inhibition in Ba/F3 cells was found to be 55 nM. [2] Inhibition of wild-type JAK2 was minimal (IC50 = 2.3 uM), such that normal marrow function is not impeded. [2, 3]

Antiproliferation activity of LY-2784544 in JAK2-V617F-driven cells was shown to be 68 nM. [2]. In Ba/F3 xenografts, LY-2784544 inhibits STAT5 phosphorylation at an threshhold effective dose (TED50) of 12.7 mg/kg. [2]