AZD1480

AZD1480 is an orally bioavailable small molecule inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), developed as a potential antineoplastic agent. By inhibiting JAK1/2, it blocks the JAK/STAT signaling pathway, including STAT3 activation, which is implicated in cancer cell proliferation and survival[1][3][4]. Preclinical studies demonstrated antiviral, immunosuppressive, anti-metastatic, and anticancer activities[5]. In clinical trials for advanced solid tumors and myeloproliferative disorders such as primary myelofibrosis and essential thrombocythaemia myelofibrosis, AZD-1480 showed rapid absorption but was associated with dose-limiting neurologic toxicities (e.g., dizziness, ataxia) that were generally reversible upon dose reduction or cessation[4]. The lack of significant clinical activity combined with its unusual toxicity profile led to discontinuation of its development as a therapeutic agent[3][4].