MA2-014

**MA2-014** is a small molecule dual-targeting inhibitor developed by Moffitt Cancer Center and licensed to Aptose Biosciences, designed to simultaneously inhibit bromodomain 4 (BRD4) and Janus kinase 2 (JAK2). It demonstrates potent anti-JAK2 activity comparable to known inhibitors like TG101209 and ruxolitinib, with approximately ten-fold greater potency against BRD4 and superior inhibition of JAK2-V617F signaling in myeloproliferative neoplasm (MPN) models. MA2-014 shows efficacy in MPN cell lines, including ruxolitinib-resistant cells, and reduces resistance development in long-term cultures of JAK2-V617F-driven UKE1 cells, positioning it as a potential single-agent combination therapy for hematologic malignancies and solid tumors.[1][3][9][12]