Pacritinib (SB1518) is a potent, selective JAK2/FLT3 inhibitor with IC50 of 23 and 19 nM for JAK2(WT) and JAK2(V617F), and IC50 of 22 nM for FLT3.
Pacritinib (SB1518) selectivity against JAK1 and JAK3 (IC(50) = 1280 and 520 nM, respectively).
Pacritinib (SB1518) shows potent effects on cellular JAK/STAT pathways, inhibiting tyrosine phosphorylation on JAK2 (Y221) and downstream STATs.
Pacritinib (SB1518) has potent anti-proliferative effects on myeloid and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3, resulting from cell cycle arrest and induction of apoptosis.
Pacritinib (SB1518) significantly reduces splenomegaly and hepatomegaly in a JAK2(V617F)-driven disease model.
Pacritinib (SB1518) dose-dependently inhibits intra-tumor JAK2/STAT5 signaling, leading to tumor growth inhibition in a subcutaneous model generated with SET-2 cells derived from a JAK2(V617F) patient with megakaryoblastic leukemia.