JAK2 inhibitors (JAK2i) are the standard treatment for myelofibrosis (MF), offering symptom relief and reducing spleen size. However, all FDA-approved JAK2i are type I inhibitors, which fail to eliminate the mutant MPN clone, leading many patients to treatment discontinuation.
Ajax Therapeutics Inc. has divulged tyrosine-protein kinase JAK2 inhibitors reported to be useful for the treatment of hematologic cancer (particularly, leukemia and lymphoma), myelofibrosis, polycythemia vera and essential thrombocythemia.
Ajax Therapeutics Inc. has received clearance for its IND application from the FDA to initiate a phase I study of AJ1‑11095, a first-in-class type II JAK2 inhibitor, for the treatment of patients with myelofibrosis.
Ajax Therapeutics Inc. has synthesized heterocyclic amide and urea compounds acting as tyrosine-protein kinase JAK2 inhibitors and thus reported to be useful for the treatment of cancer and myelofibrosis.
Type I JAK2 inhibitors improve symptoms and outcomes of patients with myeloproliferative neoplasms (MPNs), but mutant allele JAK2 VF remains unchanged with this therapy. Type II JAK2 inhibitors bind the inactive conformation of the kinase domain and reduce the fraction of JAK2 VF mutant allele in vivo, suggesting an improved approach for JAK2 inhibition. Ajax Pharmaceuticals Inc. presented preclinical data on the type II JAK2 inhibitor AJ1-10502 for the treatment of MPNs.
