ZT55, an orally active, highly-selective JAK2 inhibitor with an IC50 of 0.031 μM, inhibits proliferation of JAK2 V617F-expressing HEL cell lines, induces apoptosis and cycle arrest, and effectively inhibits HEL xenograft tumor growth in mice models. Suitable for studies on myeloproliferative neoplasms, polycythemia vera, and primary thrombocythemia, ZT55 offers promising applications.