YLIU-4-105-1 is a novel type II JAK2 inhibitor, binds to JAK2 kinase domain (JH1), show potential for overcoming acquired resistance to ruxolitinib.
YLIU-4-105-1 shows pure JAK2 selectivity, inhibits pSTAT1 (Y701) and in some cases pERK1/2 (T202/Y204) to varying extents, but does not inhibit pAKT (T308).
YLIU-4-105-1 is more potent against JAK2 V617F-dependent SET2 cells.
YLIU-4-105-1 (50 mg/kg or 75 mg/kg, IP daily) shows abdominal ascites, intraabdominal drug precipitate, and dilated loops of bowel on rhEPO-induced polycythemia mouse model.
