INCB160058 + esomeprazole

INCB160058 + esomeprazole is an investigational **combination therapy** comprising INCB160058, a highly selective inhibitor targeting the pseudokinase (JH2) domain of JAK2V617F, and esomeprazole, a proton pump inhibitor used for gastric acid suppression. INCB160058 is designed to selectively eradicate cells harboring the JAK2V617F mutation, which is commonly found in myeloproliferative neoplasms (MPNs) such as myelofibrosis, polycythemia vera, and essential thrombocythemia. Preclinical data show INCB160058 blocks ligand-independent dimerization of the thrombopoietin receptor via selective binding, leading to loss of kinase activity and normalization of proinflammatory cytokine levels, with minimal effect on wild-type JAK2 cells[1][4]. Esomeprazole is included to reduce the risk of gastrointestinal adverse events or for improved tolerability. Clinical evaluation is ongoing[2][6][1][4].