XL019

XL019 is a potent and selective small molecule inhibitor of Janus-associated kinase 2 (JAK2), with an IC50 of approximately 2 nM and over 50-fold selectivity for JAK2 compared to JAK1, JAK3, and TYK2[1][7]. It is orally bioavailable and was developed by Exelixis for the treatment of myeloproliferative disorders such as myelofibrosis and polycythemia vera[5][7]. XL019 inhibits both wild-type and mutant forms of JAK2 (including the V617F mutation), thereby blocking activation of the JAK/STAT signaling pathway—a pathway implicated in cell growth, survival, tumorigenesis, and inappropriate blood cell proliferation seen in diseases like myelofibrosis[3][5]. In addition to its primary mechanism as a JAK2 inhibitor, XL019 has been shown to inhibit P-glycoprotein (P-gp/ABCB1), potentially sensitizing drug-resistant cancer cells to antimitotic agents independently of its effects on STAT signaling[6][8]. The compound reached Phase I clinical trials but further development status is not clearly reported.

Other names

945755-56-6(S)-N-(4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)phenyl)pyrrolidine-2-carboxamideUNII-4L1AM42NVAUNII4L1AM42NVAUNII 4L1AM42NVA