AJ1-11095

AJ1-11095 is a first-in-class, orally bioavailable small molecule type II non-covalent tyrosine kinase inhibitor developed for the treatment of myelofibrosis and related myeloproliferative neoplasms. Unlike existing type I Janus kinase 2 (JAK2) inhibitors, AJ1-11095 binds both the active and inactive conformations of Janus kinase 2 (JAK2), preventing heterodimerization with Janus kinase 1 (JAK1) and Tyrosine kinase 2 (TYK2). This unique mechanism aims to overcome clonal persistence and drug resistance seen with current therapies. Preclinical studies have shown that AJ1-11095 can reverse bone marrow fibrosis, reduce mutant allele burden, and maintain efficacy against cells resistant to type I Janus kinase 2 (JAK2) inhibition. The drug was designed using advanced structure-based computational methods in collaboration between Ajax Therapeutics and Schrödinger[1][5][6][8].