JAK2 and myeloproliferative neoplasm: However, some of the major challenges of JAK2 inhibition: the first, to achieve potent catalytic inhibition without off-target effects; the second, to reach a high degree of selectivity for JAK2 against the other JAKs; the third, to specifically or preferentially target mutated forms against JAK2 WT, thus directly targeting the MPN clone and sparing normal hematopoiesis; finally, to specifically disrupt JAK2 function in defined cytokine receptor complexes were not overcame.